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Pathology of the Male and Female Reproductive System and Mammary Gland

  • Justin D. VidalEmail author
Chapter
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Abstract

Test article–related effects on the reproductive system can have a profound effect on pharmaceutical development. The reproductive system has several unique features that differ from other organ systems, including complex hormonal regulation; age-related changes such as puberty and reproductive senescence; sex-specific characteristics such as spermatogenesis in the male and cyclicity in the female; pronounced species differences; and evaluation occurring in the context of both repeated-dose general toxicology studies and stand-alone developmental and reproductive toxicology (DART) studies. This requires a broad integration of toxicology and pathology with knowledge of reproductive endocrinology, development, and comparative biology. This chapter reviews the pathology of the male and female reproductive system, including the mammary gland in females. In males, the functional anatomy and physiology are reviewed. Key issues for toxicologists, including stage-aware evaluation of spermatogenesis and sexual maturity, are discussed. Background lesions for common laboratory animals, common test article–related lesions and reversibility, ancillary testing, and issues of relevance to humans are covered. The female reproductive system and mammary gland are covered in a similar format with important issues for toxicologists including reproductive senescence and sexual maturity.

Key words

Reproduction Sexual maturity Reversibility Hormonal regulation Senescence 

References

  1. Abuelhija M, Weng CC, Shetty G, Meistrich ML (2012) Differences in radiation sensitivity of recovery of spermatogenesis between rat strains. Toxicol Sci 126(2):545–553PubMedPubMedCentralCrossRefGoogle Scholar
  2. Adams MR, Kaplan JR, Koritnik DR (1985) Psychosocial influences on ovarian endocrine and ovulatory function in Macaca fascicularis. Physiol Behav 35:935–940PubMedCrossRefPubMedCentralGoogle Scholar
  3. Ahrén K, Etienne M (1957) The development of the mammary gland in normal and castrated male rats after the age of 21 days. Acta Physiol Scand 41:283–300PubMedCrossRefPubMedCentralGoogle Scholar
  4. Alison RH, Morgan KT, Haseman JK, Boorman GA (1987) Morphology and classification of ovarian neoplasms in F344 rats and (C57BL/6 X C3H)F1 mice. J Natl Cancer Inst 78:1229–1243PubMedPubMedCentralGoogle Scholar
  5. Alison RH, Capen CC, Prentice DE (1994) Neoplastic lesions of questionable significance to humans. Toxicol Pathol 22:179–186PubMedCrossRefPubMedCentralGoogle Scholar
  6. Amann RP, Howards SS (1980) Daily spermatozoal production and epididymal spermatozoal reserves of the human male. J Urol 124(2):211–215. PubMed PMID: 6772801PubMedCrossRefPubMedCentralGoogle Scholar
  7. Amann RP, Johnson L, Thompson DL Jr, Pickett BW (1976) Daily spermatozoal production, epididymal spermatozoal reserves and transit time of spermatozoa through the epididymis of the rhesus monkey. Biol Reprod 15(5):586–592. PubMed PMID: 826287PubMedCrossRefPubMedCentralGoogle Scholar
  8. Ami Y, Suzaki Y, Goto N (1993) Endometriosis in cynomolgus monkeys retired from breeding. J Vet Med Sci 55:7–11PubMedCrossRefPubMedCentralGoogle Scholar
  9. Anderson SM, Rudolph MC, McManaman JL, Neville MC (2007) Secretory activation in the mammary gland: it’s not just about milk protein synthesis! Breast Cancer Res 9:204–217PubMedPubMedCentralCrossRefGoogle Scholar
  10. Andersson H, Tisell LE (1982) Morphology of rat prostatic lobes and seminal vesicles after long-term estrogen treatment. Acta Pathol Microbiol Immunol Scand A 90:441–448PubMedPubMedCentralGoogle Scholar
  11. Andersson H, Rydhmer L, Lundström K, Wallgren M, Andersson K, Forsberg M (1998 Apr 16) Influence of artificial light regimens on sexual maturation and boar taint in entire male pigs. Anim Reprod Sci 51(1):31–43. PubMed PMID: 9672668Google Scholar
  12. Andersson H, Rehm S, Stanislaus D, Wood CE (2013) Society of toxicologic pathology position paper: review series: assessment of circulating hormones in nonclinical toxicity studies: female reproductive hormones. Toxicol Pathol 41:921–934PubMedCrossRefPubMedCentralGoogle Scholar
  13. Andrews P, Freyberger A, Hartmann E et al (2002) Sensitive detection of the endocrine effects of the estrogen analogue ethinylestradiol using a modified enhanced subacute rat study protocol (OECD Test Guideline no. 407). Arch Toxicol 76:194–202PubMedCrossRefPubMedCentralGoogle Scholar
  14. Attia MA, Zayed I (1989) Thirteen-weeks subcutaneous treatment with high dose of natural sex hormones in rats with special reference to their effect on the pituitary-gonadal axis. I. Oestradiol. Dtsch Tierarztl Wochenschr 96:438–445PubMedPubMedCentralGoogle Scholar
  15. Bal HS, Getty R (1972) Vaginal histology of the domestic pig: histomorphology from birth to 8 years with some clinical aspects. J Reprod Fertil 28(1):1–7. PubMed PMID: 5061754PubMedCrossRefPubMedCentralGoogle Scholar
  16. Balciuniene J, Bardwell VJ, Zarkower D (2006) Mice mutant in the DM domain gene Dmrt4 are viable and fertile but have polyovular follicles. Mol Cell Biol 26:8984–8991PubMedPubMedCentralCrossRefGoogle Scholar
  17. Baldrick P, Reeve L (2007) Carcinogenicity evaluation: comparison of tumor data from dual control groups in the CD-1 mouse. Toxicol Pathol 35:562–569PubMedCrossRefPubMedCentralGoogle Scholar
  18. Bansode FW, Chowdhury SR, Dhar JD (2003) Seasonal changes in the seminiferous epithelium of rhesus and bonnet monkeys. J Med Primatol 32:170–177PubMedCrossRefPubMedCentralGoogle Scholar
  19. Barker TE, Walker BE (1966) Initiation of irreversible differentiation in vaginal epithelium. Anat Rec 154:149–160PubMedCrossRefPubMedCentralGoogle Scholar
  20. Bartlett JMS, Kerr JB, Sharpe RM (1986) The effect of selective destruction and regeneration of rat Leydig cells on the intratesticular distribution of testosterone and morphology of the seminiferous epithelium. J Androl 7:240–253PubMedCrossRefPubMedCentralGoogle Scholar
  21. Baskin GB, Smith SM, Marx PA (2002) Endometrial hyperplasia, polyps, and adenomyosis associated with unopposed estrogen in rhesus monkeys (Macaca mulatta). Vet Pathol 39:572–575PubMedCrossRefPubMedCentralGoogle Scholar
  22. Beardsley A, O’Donnell L (2003) Characterization of normal spermiation and spermiation failure induced by hormone suppression in adult rats. Biol Reprod 68:1299–1307.  https://doi.org/10.1095/biolreprod.102.009811. PMID: 12606480CrossRefPubMedPubMedCentralGoogle Scholar
  23. Beck LR (1972) Comparative observation on the morphology of the mammalian periovarial sac. J Morphol 136:247–254PubMedCrossRefPubMedCentralGoogle Scholar
  24. Beck MJ, Padgett EL, Bowman CJ et al (2006) Nonclinical juvenile toxicity testing. In: Hood RD (ed) Developmental and reproductive toxicology, 2nd edn. CRC Press, Boca Raton, pp 263–328Google Scholar
  25. Benjamin SA (2001) Epithelial mammary gland neoplasia in beagles: lifetime morbidity and mortality. In: Mohr U, Carlton WW, Dungworth DL, Benjamin SA, Capen CC, Hahn FF (eds) Pathobiology of the aging dog. Iowa State University Press, Ames, pp 179–187Google Scholar
  26. Ben-Jonathan N, LaPensee CR, LaPensee EW (2008) What can we learn from rodents about prolactin in humans? Endocr Rev 29:1–41PubMedCrossRefPubMedCentralGoogle Scholar
  27. Berg BN (1967) Longevity studies in rats. II. Pathology of ageing rats. In: Cotchin E, Roe FJC (eds) Pathology of laboratory rats and mice. Blackwell Scientific Publications, Oxford, pp 749–786Google Scholar
  28. Berman DM, Tian H, Russell DW (1995) Expression and regulation of steroid 5 alpha-reductase in the urogenital tract of the fetal rat. Mol Endocrinol 9:1561–1570PubMedPubMedCentralGoogle Scholar
  29. Bhatti SFM, Rao NAS, Okkens AC et al (2007) Role of progestin-induced mammary-derived growth hormone in the pathogenesis of cystic endometrial hyperplasia in the bitch. Domest Anim Endocrinol 33:294–312PubMedCrossRefPubMedCentralGoogle Scholar
  30. Bhowmik T, Mukherjea M (1988) Changes in the ovary and uterus of rat after injectable contraceptive therapy. Contraception 37:529–538PubMedCrossRefPubMedCentralGoogle Scholar
  31. Biegel LB, Flaws JA, Hirshfield AN et al (1998) 90-day feeding and one-generation reproduction study in Crl:CD BR rats with 17 beta-estradiol. Toxicol Sci 44:116–142PubMedPubMedCentralGoogle Scholar
  32. Blanchard KT, Lee J, Boekelheide K (1998) Leuprolide, a gonadotropin-releasing hormone agonist, reestablishes spermatogenesis after 2,5-hexanedione-induced irreversible testicular injury in the rat, resulting in normalized stem cell factor expression. Endocrinology 139(1):236–244. PubMed PMID: 9421420PubMedCrossRefPubMedCentralGoogle Scholar
  33. Bode G, Clausing P, Gervais F, Loegsted J, Luft J, Nogues V, Sims J, Steering Group of the RETHINK Project (2010) The utility of the minipig as an animal model in regulatory toxicology. J Pharmacol Toxicol Methods 62(3):196–220.  https://doi.org/10.1016/j.vascn.2010.05.009. Epub 2010 May 31. Review. PubMed PMID: 20685310CrossRefPubMedPubMedCentralGoogle Scholar
  34. Bonneau M, Carrie-Lemoine J, Prunier A, Garnier DH, Terqui M (1987) Age-related changes in plasma LH and testosterone concentration profiles and fat 5α-androstenone content in the young boar. Anim Reprod Sci 15(3–4):241–258CrossRefGoogle Scholar
  35. Boorman GA, Wilson JT, van Zwieten MJ, Eustis SL (1990) Mammary gland. In: Boorman GA, Eustis SL, Elwell MR, Montgomery CA Jr, MacKenzie WF (eds) Pathology of the Fischer rat. Academic Press, San Diego, pp 295–313Google Scholar
  36. Borovskaya TG, Goldberg VE, Fomina TI et al (2004) Morphological and functional state of rat ovaries in early and late periods after administration of platinum cytostatics. Bull Exp Biol Med 137:331–335PubMedCrossRefPubMedCentralGoogle Scholar
  37. Bouchard GF, Solorzano N, Concannon PW, Youngquist RS, Bierschwal CJ (1991) Determination of ovulation time in bitches based on teasing, vaginal cytology, and elisa for progesterone. Theriogenology 35(3):603–611. PubMed PMID: 16726929PubMedCrossRefPubMedCentralGoogle Scholar
  38. Brinkworth MH, Weinbauer GF, Schlatt S, Nieschlag E (1995) Identification of male germ cells undergoing apoptosis in male rats. J Reprod Fertil 105:25–33PubMedCrossRefPubMedCentralGoogle Scholar
  39. Brisken C, O’Malley B (2010) Hormone action in the mammary gland. Cold Spring Harb Perspect Biol 2:a003178PubMedPubMedCentralCrossRefGoogle Scholar
  40. Brisken C, Rajaram RD (2006) Alveolar and lactogenic differentiation. J Mammary Gland Biol Neoplasia 11:239–248PubMedCrossRefPubMedCentralGoogle Scholar
  41. Brix A, Nyska A, Haseman JK, Sells DM, Jokinen MP, Walker NJ (2005) Incidences of selected lesions in control female Harlan Sprague-Dawley rats from two-year studies performed by the National Toxicology Program. Toxicol Pathol 33:477–483PubMedCrossRefPubMedCentralGoogle Scholar
  42. Bristol-Gould S, Woodruff TK (2006) Folliculogenesis in the domestic cat (Felis catus). Theriogenology 66:5–13PubMedCrossRefPubMedCentralGoogle Scholar
  43. Brown HR, Leininger JR (1992) Alterations of the uterus. In: Mohr U, Dungworth DL, Capen CC (eds) Pathobiology of the aging rat, vol 1. ILSI Press, Washington, DC, pp 377–388Google Scholar
  44. Brown AP, Morrissey RL, Crowell JA, Levine BS (1999a) Thirteen-week oral toxicity study of difluoromethylornithine in combination with tamoxifen citrate in female dogs. Cancer Chemother Pharmacol 43:479–488PubMedCrossRefPubMedCentralGoogle Scholar
  45. Brown AP, Morrissey RL, Crowell JA, Levine BS (1999b) Difluoromethylornithine in combination with tamoxifen in female rats: 13-week oral toxicity study. Cancer Chemother Pharmacol 44:475–483PubMedCrossRefPubMedCentralGoogle Scholar
  46. Bruner R, Küttler K, Bader R et al (2001) Integumentary system. In: Mohr U (ed) International classification of rodent tumors: the mouse. Springer-Verlag, Berlin, pp 1–22Google Scholar
  47. Buse E, Zöller M, van Esch E (2008) The macaque ovary, with special reference to the cynomolgus macaque (Macaca fascicularis). Toxicol Pathol 36:24S–66SCrossRefGoogle Scholar
  48. Cardiff RD, Wellings SR (1999) The comparative pathology of human and mouse mammary glands. J Mammary Gland Biol Neoplasia 4:105–122PubMedCrossRefPubMedCentralGoogle Scholar
  49. Cardy RH (1991) Sexual dimorphism of the normal rat mammary gland. Vet Pathol 28:139–145PubMedCrossRefPubMedCentralGoogle Scholar
  50. Carthew P, Edwards RE, Nolan BM, Martin EA, Smith LL (1996) Tamoxifen associated uterine pathology in rodents: relevance to women. Carcinogenesis 17:1577–1582PubMedCrossRefPubMedCentralGoogle Scholar
  51. Cartwright J, Moreland S (2008) Endocrine disruption: a guidance document for histologic evaluation of endocrine and reproductive tests. Part 3e: Female reproductive system. Morphological patterns of endocrine disruption. Organization of Economic Cooperation and Development. http://www.oecd.org/dataoecd/30/19/43754876.pdf
  52. Chambô-Filho A, Camargos AF, Pereira FEL (2005) Morphological changes induced by testosterone in the mammary glands of female Wistar rats. Braz J Med Biol Res 38:553–558PubMedCrossRefPubMedCentralGoogle Scholar
  53. Chan TW, Pollack M, Huynh H (2001) Inhibition of insulin-like growth factor signaling pathways in mammary gland by pure antiestrogen ICI 182,780. Clin Cancer Res 7:2545–2554PubMedPubMedCentralGoogle Scholar
  54. Chandra SA, Adler RA (2008) Frequency of different estrus stages in purpose-bred beagles: a retrospective study. Toxicol Pathol 36:944–949PubMedCrossRefPubMedCentralGoogle Scholar
  55. Chandra SA, Cline JM, Adler RR (2010) Cyclic morphological changes in the beagle mammary gland. Toxicol Pathol 38:969–983PubMedCrossRefPubMedCentralGoogle Scholar
  56. Chapin RE, Creasy DM (2012) Assessment of circulating hormones in regulatory toxicity studies II. Male reproductive hormones. Toxicol Pathol 40:1063–1078PubMedCrossRefPubMedCentralGoogle Scholar
  57. Chapin RE, White RD, Morgan KT, Bus JS (1984) Studies of lesions induced in the testis and epididymis of F-344 rats by inhaled methyl chloride. Toxicol Appl Pharmacol 76:328–343PubMedCrossRefPubMedCentralGoogle Scholar
  58. Chatani F (2006) Possible mechanism for testicular focal necrosis induced by hCG in rats. J Toxicol Sci 31(4):291–303. PubMed PMID: 17077584PubMedCrossRefPubMedCentralGoogle Scholar
  59. Chen H, Stanley E, Jin S, Zirkin B (2010) Stem Leydig cells: from fetal to aged animals. Birth Defects Res C Embryo Today 90:272–283PubMedPubMedCentralCrossRefGoogle Scholar
  60. Clegg ED, Cook JC, Chapin RE, Foster PMD, Daston GP (1997) Leydig cell hyperplasia and adenoma formation: mechanisms and relevance to humans. Reprod Toxicol 11:107–121PubMedCrossRefPubMedCentralGoogle Scholar
  61. Clemo FAS, Evering WE, Snyder PW, Albassam MA (2003) Differentiating spontaneous from drug-induced vascular injury in the dog. Toxicol Pathol 31(Suppl):25–31PubMedCrossRefPubMedCentralGoogle Scholar
  62. Clermont Y (1972) Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev 52:198–236PubMedPubMedCentralCrossRefGoogle Scholar
  63. Clifton DK, Bremner WJ (1983) The effect of testicular x-irradiation on spermatogenesis in man. A comparison with the mouse. J Androl 4(6):387–392PubMedCrossRefPubMedCentralGoogle Scholar
  64. Cline JM, Franke AA, Register TC, Golden DL, Adams MR (2004) Effects of dietary isoflavone aglycones on the reproductive tract of male and female mice. Toxicol Pathol 32:91–99PubMedCrossRefPubMedCentralGoogle Scholar
  65. Cline JM (2007) Assessing the mammary gland of nonhuman primates: effects of endogenous hormones and exogenous hormonal agents and growth factors. Birth Defects Res B Dev Reprod Toxicol 80:126–146PubMedCrossRefPubMedCentralGoogle Scholar
  66. Cline JM, Wood CE (2008) The mammary glands of macaques. Toxicol Pathol 36:130S–141SCrossRefGoogle Scholar
  67. Cline JM, Soderqvist G, von Schoultz E, Skoog L, von Schoultz B (1998) Effects of conjugated estrogens, medroxyprogesterone acetate, and tamoxifen on the mammary glands of macaques. Breast Cancer Res Treat 48:221–229PubMedCrossRefPubMedCentralGoogle Scholar
  68. Cline JM, Wood CE, Vidal JD, Tarara RP, Buse E, Weinbauer GF, de Rijk EPCT, van Esch E (2008) Selected background findings and interpretation of common lesions in the female reproductive system in macaques. Toxicol Pathol 36:142S–163SPubMedPubMedCentralCrossRefGoogle Scholar
  69. Cohen I, Sims ML, Robbins MR, Lakshmanan MC, Francis PC, Long GG (2000) The reversible effects of raloxifene on luteinizing hormone levels and ovarian morphology in mice. Reprod Toxicol 14:37–44PubMedCrossRefPubMedCentralGoogle Scholar
  70. Concannon PW (2009) Endocrinologic control of normal canine ovarian function. Reprod Domest Anim 44:3–15PubMedCrossRefPubMedCentralGoogle Scholar
  71. Concannon PW (2011) Reproductive cycles of the bitch. Anim Reprod Sci 124:200–210PubMedCrossRefPubMedCentralGoogle Scholar
  72. Concannon PW, Hansel W, Visek WJ (1975) The ovarian cycle of the bitch: plasma estrogen, LH and progesterone. Biol Reprod 13:112–121PubMedCrossRefPubMedCentralGoogle Scholar
  73. Concannon PW, Spraker TR, Casey HW, Hansel W (1981) Gross and histopathologic effects of medroxyprogesterone acetate and progesterone on the mammary glands of adult beagle bitches. Fertil Steril 36:373–387PubMedCrossRefPubMedCentralGoogle Scholar
  74. Concannon PW, McCann JP, Temple M (1989) Biology and endocrinology of ovulation, pregnancy and parturition in the dog. J Reprod Fertil Suppl 39:3–25PubMedPubMedCentralGoogle Scholar
  75. Cook JC, Klinefelter GR, Hardisty JF, Sharpe RM, Foster PMD (1999) Rodent Leydig cell tumorigenesis: a review of the physiology, pathology, mechanisms, and relevance to humans. Crit Rev Toxicol 29:169–261PubMedCrossRefPubMedCentralGoogle Scholar
  76. Cooper TK, Gabrielson KL (2007) Spontaneous lesions in the reproductive tract and mammary gland of female non-human primates. Birth Defects Res B Dev Reprod Toxicol 80:149–170PubMedCrossRefPubMedCentralGoogle Scholar
  77. Cora MC, Kooistra L, Travlos G (2015 Aug) Vaginal cytology of the laboratory rat and mouse: review and criteria for the staging of the estrous cycle using stained vaginal smears. Toxicol Pathol 43(6):776–793.  https://doi.org/10.1177/0192623315570339. Epub 2015 Mar 3. Review. PubMed PMID: 25739587
  78. Creasy DM (1997) Evaluation of testicular toxicity in safety evaluation studies: the appropriate use of spermatogenic staging. Toxicol Pathol 25:119–131PubMedCrossRefPubMedCentralGoogle Scholar
  79. Creasy DM (2001) Pathogenesis of male reproductive toxicity. Toxicol Pathol 29:64–76PubMedCrossRefPubMedCentralGoogle Scholar
  80. Creasy D (2008a) Endocrine disruption: a guidance document for histologic evaluation of endocrine and reproductive tests. Part 2: Male reproductive system. Organization of Economic Cooperation and Development. http://www.oecd.org/dataoecd/29/35/43754701.pdf
  81. Creasy D (2008b) Endocrine disruption: a guidance document for histologic evaluation of endocrine and reproductive tests. Part 4: Mammary gland. Organization of Economic Cooperation and Development. http://www.oecd.org/dataoecd/30/20/43754898.pdf
  82. Creasy D (2012) Reproduction of the rat, mouse, dog, non-human primate and minipig. In: McInnes EF (ed) Background lesions in laboratory animals: a color atlas. Saunders Elsevier, Edinburgh, pp 109–110Google Scholar
  83. Creasy DM, Chapin RE (2013) Male reproductive system. In: Haschek WM, Rousseaux CG, Wallig MA, Bolon B, Ochoa R, Mahler BW (eds) Haschek and Rousseaux’s handbook of toxicologic pathology, 3rd edn. Elsevier, London, pp 2493–2598CrossRefGoogle Scholar
  84. Creasy D, Bube A, de Rijk E, Kandori H, Kuwahara M, Masson R, Nolte T, Reams R, Regan K, Rehm S, Rogerson P, Whitney K (2012) Proliferative and nonproliferative lesions of the rat and mouse male reproductive system. Toxicol Pathol 40(6 Suppl):40S–121SPubMedCrossRefPubMedCentralGoogle Scholar
  85. Cross BA, Goodwin RF, Silver IA (1958 May) A histological and functional study of the mammary gland in normal and agalactic sows. J Endocrinol 17(1):63–74Google Scholar
  86. Czoty PW, Gould RW, Nader MA (2009) Relationship between social rank and cortisol and testosterone concentration in male cynomolgus monkeys (Macaca fascicularis). J Neuroendocrinol 21:68–76PubMedPubMedCentralCrossRefGoogle Scholar
  87. Daly TJ, Kramer B (1998) Alterations in rat vaginal histology by exogenous gonadotrophins. J Anat 193:469–472PubMedPubMedCentralCrossRefGoogle Scholar
  88. Damm Jorgensen KD (1998) Minipig in reproduction toxicology. Scand J Lab Anim Sci 25:63–75Google Scholar
  89. Daane TA, Lyons WR (1954) Effect of estrone, progesterone and pituitary mammotropin on the mammary glands of castrated C3H male mice. Endocrinology 55:191–199PubMedCrossRefPubMedCentralGoogle Scholar
  90. Daniel CW, Silberstein GB (1987) Postnatal development of the rodent mammary gland. In: Neville MC, Daniel CW (eds) The mammary gland. Plenum Press, New York, pp 3–36CrossRefGoogle Scholar
  91. Darney KJ Jr, Goldman JM, Vandenbergh JG (1992) Neuroendocrine responses to social regulation of puberty in the female house mouse. Neuroendocrinology 55(4):434–443.  https://doi.org/10.1159/000126155CrossRefPubMedPubMedCentralGoogle Scholar
  92. Davis B, Fenton S (2013) Chapter 61: Mammary gland. In: Haschek WM, Rousseaux CG, Wallig MA, Ochoa R, Bolon B (eds) Haschek and Rousseaux’s handbook of toxicologic pathology, vol 3, 3rd edn. Elsevier, Academic Press, Amsterdam, pp 2665–2694CrossRefGoogle Scholar
  93. Davis B, Almekinder J, Flagler N, Travlos G, Wilson R, Maronpot RR (1997) Ovarian luteal cell toxicity of ethylene glycol monomethyl ether and methoxy acetic acid in vivo and in vitro. Toxicol Appl Pharmacol 142:328–337PubMedCrossRefPubMedCentralGoogle Scholar
  94. Davis BJ, Dixon D, Herbert RA (1999) Ovary, oviduct, uterus, cervix, and vagina. In: Maronpot RR (ed) Pathology of the mouse. Cache River Press, Vienna, pp 409–443Google Scholar
  95. De Grava Kempinas W, Klinefelter GR (2014) Interpreting histopathology in the epididymis. Spermatogenesis 4(2):e979114.  https://doi.org/10.4161/21565562.2014.979114CrossRefPubMedPubMedCentralGoogle Scholar
  96. de Rijk E, van den Brink H, Lensen J, Lambregts A, Lorentsen H, Peter B (2014) Estrous cycle-dependent morphology in the reproductive organs of the female Göttingen minipig. Toxicol Pathol 42(8):1197–1211.  https://doi.org/10.1177/0192623314526136. Epub 2014 Mar 26. PubMed PMID: 24670815CrossRefPubMedPubMedCentralGoogle Scholar
  97. De Schaepdrijver LM, Fransen JL, Van der Eycken ES, Coussement WC (1995) Transverse vaginal septum in the specific-pathogen-free Wistar rat. Lab Anim Sci 45:181–183PubMedPubMedCentralGoogle Scholar
  98. Dirami G, Teerds KJ, Cooke BA (1996) Effect of dopamine agonist on the development of Leydig cell hyperplasia in Sprague-Dawley rats. Toxicol Appl Pharmacol 141:169–177. PMID: 8917689PubMedCrossRefPubMedCentralGoogle Scholar
  99. Dixon D, Leininger JR, Valerio MG, Johnson AN, Stabinski LG, Frith CH (1999) Proliferative lesions of the ovary, uterus, vagina, cervix and oviduct in rats, URG-5. In: Guides for toxicologic pathology. STP/ARP/AFIP, Washington DCGoogle Scholar
  100. Dixon D, Alison R, Bach U, Colman K, Foley GL, Harleman JH, Haworth R, Herbert R, Heuser A, Long G, Mirsky M, Regan K, van Esch E, Westwood FR, Vidal J, Yoshida M (2014) Nonproliferative and proliferative lesions of the rat and mouse female reproductive system. J Toxicol Pathol 27:1S–107SPubMedPubMedCentralCrossRefGoogle Scholar
  101. Dorso LF, Chanut PH, Burnett R (2008) Variability in weight and histologic appearance of the prostate of beagle dogs used in toxicology studies. Toxicol Pathol 36:917–925PubMedCrossRefPubMedCentralGoogle Scholar
  102. Downs JL, Wise PM (2009) The role of the brain in female reproductive aging. Mol Cell Endocrinol 299:32–38PubMedCrossRefPubMedCentralGoogle Scholar
  103. Dreef HC, van Esch E, de Rijk EPCT (2007) Spermatogenesis in the cynomolgus monkey (Macaca fascicularis): a practical guide for routine morphological staging. Toxicol Pathol 35:395–404PubMedCrossRefPubMedCentralGoogle Scholar
  104. Duncan MK, Chada KK (1993) Incidence of tubulostromal adenoma of the ovary in aged germ cell-deficient mice. J Comp Pathol 109:13–19PubMedCrossRefPubMedCentralGoogle Scholar
  105. Dürnberger H, Kratochwil K (1980) Specificity of tissue interaction and origin of mesenchymal cells in the androgen response of the embryonic mammary gland. Cell 19:465–471PubMedCrossRefPubMedCentralGoogle Scholar
  106. Einarsson S, Andersson K, Wallgren M, Lundström K, Rodriguez-Martinez H (2009) Short- and long-term effects of immunization against gonadotropin-releasing hormone, using Improvac, on sexual maturity, reproductive organs and sperm morphology in male pigs. Theriogenology 71(2):302–310.  https://doi.org/10.1016/j.theriogenology.2008.07.022. Epub 2008 Aug 31. PubMed PMID: 18762333CrossRefPubMedPubMedCentralGoogle Scholar
  107. El Etreby MF (1979) Effect of cyproteroneacetate, levorgenestrol and progesterone on adrenal glands and reproductive organs in the beagle bitch. Cell Tissue Res 200:229–243PubMedCrossRefPubMedCentralGoogle Scholar
  108. El Etreby MF, Gräf KJ (1979) Effect of contraceptive steroids on mammary gland of beagle dog and its relevance to human carcinogenicity. Pharmacol Ther 5:369–402CrossRefGoogle Scholar
  109. Eliasson L (1989) A study on puberty and oestrus in gilts. Zentralbl Veterinarmed A 36(1):46–54. PubMed PMID: 2497607PubMedCrossRefPubMedCentralGoogle Scholar
  110. Ellis GB, Desjardins C (1982) Male rats secrete luteinizing hormone and testosterone episodically. Endocrinology 110:1618–1627PubMedCrossRefPubMedCentralGoogle Scholar
  111. Evans B, Gannon BJ, Heath JW, Burnstock G (1977) Long lasting damage to the internal male genital organs and their adrenergic innervations in rats following chronic treatment with the antihypertensive drug guanethidine. Fertil Steril 23:657–667CrossRefGoogle Scholar
  112. Everds NE, Snyder PW, Bailey KL, Bolon B, Creasy DM, Foley GL, Rosol TJ, Sellers T (2013) Interpreting stress responses during routine toxicity studies: a review of the biology, impact, and assessment. Toxicol Pathol 41(4):560–614.  https://doi.org/10.1177/0192623312466452. Epub 2013 Mar 7. Review. PubMed PMID: 23475558CrossRefPubMedPubMedCentralGoogle Scholar
  113. Ezer N, Robaire B (2002) Androgenic regulation of the structure and function of the epididymis. In: Robaire B, Hinton BT (eds) The epididymis: from molecules to clinical practice. Kluwer Academic/Plenum Publishers, New York, pp 297–316CrossRefGoogle Scholar
  114. Fanton JW, Hubbard GB, Wood DH (1986) Endometriosis: clinical and pathologic findings in 70 rhesus monkeys. Am J Vet Res 47(7):1537–1541. PubMed PMID: 3740623PubMedPubMedCentralGoogle Scholar
  115. Farmer C (2013) Mammary development in swine: effects of hormonal status, nutrition and management. Can J Anim Sci 93(1):1–7CrossRefGoogle Scholar
  116. Fawcett DW, Neaves WB, Flores MN (1973) Comparative observations on intertubular lymphatics and the organization of the interstitial tissue of the mammalian testis. Biol Reprod 9:500–532PubMedCrossRefPubMedCentralGoogle Scholar
  117. Felicio LS, Nelson JF, Finch CE (1984) Longitudinal studies of estrous cyclicity in aging C57BL/6J mice: II. Cessation of cyclicity and the duration of persistent vaginal cornification. Biol Reprod 31:446–453PubMedCrossRefPubMedCentralGoogle Scholar
  118. Ferrara N, Chen H, Davis-Smyth T, Gerber HP, Nguyen TN, Peers D, Chisholm V, Hillan KJ, Schwall RH (1998) Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat Med 4:336–340PubMedCrossRefPubMedCentralGoogle Scholar
  119. Flickinger CJ, Howard SS (2002) Consequences of obstruction on the epididymis. In: Robaire B, Hinton BT (eds) The epididymis: from molecules to clinical practice. Kluwer Academic/Plenum Publishers, New York, pp 503–522CrossRefGoogle Scholar
  120. Foley GL (2001) Overview of male reproductive pathology. Toxicol Pathol 29:49–63PubMedCrossRefPubMedCentralGoogle Scholar
  121. Foley GL, Bassily N, Hess RA (1995) Intratubular spermatic granulomas of the canine efferent ductules. Toxicol Pathol 23:731–735PubMedCrossRefPubMedCentralGoogle Scholar
  122. Foote RH, Swierstra EE, Hunt WL (1972) Spermatogenesis in the dog. Anat Rec 173(3):341–351. PubMed PMID: 5039087PubMedCrossRefPubMedCentralGoogle Scholar
  123. Ford JJ (1983) Serum estrogen concentrations during postnatal development in male pigs. Proc Soc Exp Biol Med 174(2):160–164PubMedCrossRefPubMedCentralGoogle Scholar
  124. Ford JJ, Wise TH (2011) Assessment of pubertal development of boars derived from ultrasonographic determination of testicular diameter. Theriogenology 75(2):241–247.  https://doi.org/10.1016/j.theriogenology.2010.08.010. Epub 2010 Oct 18CrossRefPubMedPubMedCentralGoogle Scholar
  125. Förster C, Mäkela S, Wärri A et al (2002) Involvement of estrogen receptor beta in terminal differentiation of mammary gland epithelium. Proc Natl Acad Sci U S A 99:15578–15583PubMedPubMedCentralCrossRefGoogle Scholar
  126. Fortune JE (1994) Ovarian follicular growth and development in mammals. Biol Reprod 50:225–232PubMedCrossRefPubMedCentralGoogle Scholar
  127. Fouquet JP, Dadoune JP (1986) Renewal of spermatogonia in the monkey (Macaca fascicularis). Biol Reprod 35(1):199–207. PubMed PMID: 3741951PubMedCrossRefPubMedCentralGoogle Scholar
  128. Fowler KA, Gill K, Kirma N, Dillehay DL, Tekmal RR (2000) Overexpression of aromatase leads to development of testicular Leydig cell tumors. Am J Pathol 156:347–353PubMedPubMedCentralCrossRefGoogle Scholar
  129. França LR, Silva VA Jr, Chiarini-Garcia H, Garcia SK, Debeljuk L (2000) Cell proliferation and hormonal changes during postnatal development of the testis in the pig. Biol Reprod 63(6):1629–1636PubMedCrossRefPubMedCentralGoogle Scholar
  130. França LR, Avelar GF, Almeida FF (2005) Spermatogenesis and sperm transit through the epididymis in mammals with emphasis on pigs. Theriogenology 63(2):300–318. Review. PubMed PMID: 15626401PubMedCrossRefPubMedCentralGoogle Scholar
  131. Freeman ME (2006) Neuroendocrine control of the ovarian cycle in the rat. In: Neill JD (ed) Knobil and Neill’s physiology of reproduction, 3rd edn. Elseveier, San Diego, pp 2327–2388CrossRefGoogle Scholar
  132. Ganderup NC (2014) Minipig models for toxicity and biomarker testing. In: Gupta RC (ed) Biomarkers in toxicology. Elsevier, AmsterdamGoogle Scholar
  133. Gao HB, Tong MH, Hu YQ, Guo QS, Ge R, Hardy MP (2002) Glucocorticoid induces apoptosis in rat Leydig cells. Endocrinology 143:130–138PubMedCrossRefPubMedCentralGoogle Scholar
  134. Gaytán F, Bellido C, Gaytán M, Morales C, Sánchez-Criado JE (2003) Differential effects of RU486 and indomethacin on follicle rupture during the ovulatory process in the rat. Biol Reprod 69:99–105PubMedCrossRefPubMedCentralGoogle Scholar
  135. Gaytán F, Morales C, Leon S et al (2017) Development and validation of a method for precise dating of female puberty in laboratory rodents: the puberty ovarian maturation score (Pub-Score). Sci Rep 7:46381.  https://doi.org/10.1038/srep46381CrossRefPubMedPubMedCentralGoogle Scholar
  136. Generoso WM, Stout SK, Huff SW (1971) Effects of alkylating chemicals on reproductive capacity of adult female mice. Mutat Res 13:171–184CrossRefGoogle Scholar
  137. Geschickter CF, Hartman CG (1959) Mammary response to prolonged estrogenic stimulation in the monkey. Cancer 12:767–781PubMedCrossRefPubMedCentralGoogle Scholar
  138. Goedkin MJ, Kerlin RL, Morton D (2008) Spontaneous and age-related testicular findings in beagle dogs. Toxicol Pathol 36:465–471CrossRefGoogle Scholar
  139. Goldman JM, Murr AS, Cooper RL (2007) The rodent estrous cycle: characterization of vaginal cytology and its utility in toxicological studies. Birth Defects Res B Dev Reprod Toxicol 80:84–97PubMedCrossRefPubMedCentralGoogle Scholar
  140. Goldschmidt M, Peña L, Rasotto R, Zappulli V (2011) Classification and grading of canine mammary tumors. Vet Pathol 48:117–131PubMedCrossRefPubMedCentralGoogle Scholar
  141. Gondos B, Berndtson WE (1993) Postnatal and pubertal development. In: Russell LD, Griswold MD (eds) The Sertoli cell. Cache River Press, Clearwater, pp 115–154Google Scholar
  142. Gopinath C (1992) Susceptibility of the uterus to toxic substances. In: Mohr U, Dungworth DL, Capen CC (eds) Pathobiology of the aging rat, vol 1. ILSI Press, Washington, DC, pp 389–394Google Scholar
  143. Gopinath C, Gibson WA (1987) Mesovarian leiomyomas in the rat. Environ Health Perspect 73:107–113PubMedPubMedCentralCrossRefGoogle Scholar
  144. Gore AC, Oung T, Yung S, Flagg RA, Woller MJ (2000) Neuroendocrine mechanisms for reproductive senescence in the female rat. Endocrine 13:315–323PubMedCrossRefPubMedCentralGoogle Scholar
  145. Gotoh Y, Netsu J, Nakai M, Nasu T (1999) Testicular damage after exposure to carbendazim depends on the number of patent efferent ductules. J Vet Med Sci 61:755–760PubMedCrossRefPubMedCentralGoogle Scholar
  146. Gouletsou PG, Galatos AD, Leontides LS (2008) Comparison between ultrasonographic and caliper measurements of testicular volume in the dog. Anim Reprod Sci 108(1–2):1–12. Epub 2007 Jun 23PubMedCrossRefPubMedCentralGoogle Scholar
  147. Gräf KJ (1978) Serum oestrogen, progesterone and prolactin concentrations in cyclic, pregnant and lactating beagle dogs. J Reprod Fertil 52:9–14PubMedCrossRefPubMedCentralGoogle Scholar
  148. Graham CE (1970) Response of the rhesus monkey uterine cervix to chronic estrogenic stimulation. Am J Obstet Gynecol 108:1192–1196PubMedCrossRefPubMedCentralGoogle Scholar
  149. Greaves P (2007) Histopathology of preclinical toxicity studies, 3rd edn. Academic Press, New YorkGoogle Scholar
  150. Greaves P, Faccini JM (1984) Rat histopathology. A glossary for use in toxicity and carcinogenicity studies. Elsevier, Amsterdam, pp 171–186Google Scholar
  151. Greaves P, White INH (2006) Experimental adenomyosis. Best Pract Res Clin Obstet Gynaecol 20:503–510PubMedCrossRefPubMedCentralGoogle Scholar
  152. Greaves P, Goonetilleke R, Nunn G, Topham J, Orton T (1993) Two-year carcinogenicity study of tamoxifen in Alderley Park Wistar-derived rats. Cancer Res 53:3919–3924PubMedPubMedCentralGoogle Scholar
  153. Greenman DL, Fullerton FR (1986) Comparison of histological responses of BALB/c and B6C3F1 female mice to estradiol when fed purified or natural-ingredient diets. J Toxicol Environ Health 19:531–540PubMedCrossRefPubMedCentralGoogle Scholar
  154. Greenman DL, Gaylor D, Highman B, Farmer J, Norvell MJ, Gass G (1983) Nonneoplastic changes induced in female C3H mice by chronic exposure to diethylstilbestrol or 17 beta-estradiol. J Toxicol Environ Health 11:843–856PubMedCrossRefPubMedCentralGoogle Scholar
  155. Grosser PM, McCarthy GF, Robaire B, Farookhi R, Brawer JR (1987) Plasma patterns of LH, FSH and prolactin in rats with a polycystic ovarian condition induced by oestradiol valerate. J Endocrinol 114:33–39PubMedCrossRefPubMedCentralGoogle Scholar
  156. Gunn SA, Gould TC, Anderson WAD (1963) The selective injurious response of testicular and epididymal blood vessels to cadmium and its prevention by zinc. Am J Pathol 42:685–702PubMedPubMedCentralGoogle Scholar
  157. Habenicht UF, el Etreby MF (1988) The periurethral zone of the prostate of the cynomolgus monkey is the most sensitive prostate part for an estrogenic stimulus. Prostate 13(4):305–316. PubMed PMID: 2464165PubMedCrossRefPubMedCentralGoogle Scholar
  158. Hadfield RM, Yudkin PL, Coe CL, Scheffler J, Uno H, Barlow DH, Kemnitz JW, Kennedy SH (1997) Risk factors for endometriosis in the rhesus monkey (Macaca mulatta): a case-control study. Hum Reprod Update 3:109–115PubMedCrossRefPubMedCentralGoogle Scholar
  159. Hall JM, Couse JF, Korach KS (2001) The multifaceted mechanisms of estradiol and estrogen receptor signaling. J Biol Chem 276:36869–36872PubMedCrossRefPubMedCentralGoogle Scholar
  160. Hall AP, Ashton S, Horner J, Wilson Z, Reens J, Richmond GH, Barry ST, Wedge SR (2016) PDGFR inhibition results in pericyte depletion and hemorrhage into the corpus luteum of the rat ovary. Toxicol Pathol 44:98–111PubMedCrossRefPubMedCentralGoogle Scholar
  161. Halpern WG, Ameri M, Bowman CJ, Elwell MR, Mirsky ML, Oliver J, Regan KS, Remick AK, Sutherland VL, Thompson KE, Tremblay C, Yoshida M, Tomlinson L (2016) Scientific and regulatory policy committee points to consider review: inclusion of reproductive and pathology end points for assessment of reproductive and developmental toxicity in pharmaceutical drug development. Toxicol Pathol 44:789–809PubMedPubMedCentralCrossRefGoogle Scholar
  162. Harleman JH, Hargreaves A, Andersson H, Kirk S (2012) A review of the incidence and coincidence of uterine and mammary tumors in Wistar and Sprague-Dawley rats based on the RITA database and the role of prolactin. Toxicol Pathol 40:926–930PubMedCrossRefPubMedCentralGoogle Scholar
  163. Harneit S, Paust HJ, Mukhopadhyay AK, Ergun S (1997) Localization of endothelin 1 and endothelin receptors A and B in human epididymis. Mol Hum Reprod 3:579–584PubMedCrossRefPubMedCentralGoogle Scholar
  164. Haruyama E, Suda M, Ayukawa Y et al (2012) Testicular development in cynomolgus monkeys. Toxicol Pathol 40:935–942PubMedCrossRefPubMedCentralGoogle Scholar
  165. Harvell DME, Strecker TE, Tochacek M et al (2000) Rat strain-specific actions of 17β-estradiol in the mammary gland: correlation between estrogen-induced lobuloalveolar hyperplasia and susceptibility to estrogen-induced mammary cancers. Proc Natl Acad Sci U S A 97:2779–2784PubMedPubMedCentralCrossRefGoogle Scholar
  166. Helke KL, Nelson KN, Sargeant AM, Jacob B, McKeag S, Haruna J, Vemireddi V, Greeley M, Brocksmith D, Navratil N, Stricker-Krongrad A, Hollinger C (2016 Apr) Background pathological changes in minipigs: a comparison of the incidence and nature among different breeds and populations of minipigs. Toxicol Pathol 44(3):325–337.  https://doi.org/10.1177/0192623315611762. Epub 2015 Nov 3. PubMed PMID: 26534940
  167. Hess RA (1990) Quantitative and qualitative characteristics of the stages and transitions in the cycle of the rat seminiferous epithelium: light microscopic observation of perfusion-fixed and plastic embedded testes. Biol Reprod 43:525–542PubMedCrossRefPubMedCentralGoogle Scholar
  168. Hess RA (2002) The efferent ductules: structure and function. In: Robaire B, Hinton BT (eds) The epididymis: from molecules to clinical practice. Kluwer Academic/Plenum Publishers, New York, pp 49–80CrossRefGoogle Scholar
  169. Hess RA (2014) Disruption of estrogen receptor signaling and similar pathways in the efferent ductules and initial segment of the epididymis. Spermatogenesis 4(2):e979103PubMedPubMedCentralCrossRefGoogle Scholar
  170. Hess RA, Nakai M (2000) Histopathology of the male reproductive system induced by the fungicide benomyl. Histol Histopathol 15:207–224PubMedPubMedCentralGoogle Scholar
  171. Hess RA, Zhou Q, Nie R (2002) The role of estrogens in the endocrine and paracrine regulation of the efferent ductules, epididymis and vas deferens. In: Robaire B, Hinton BT (eds) The epididymis: from molecules to clinical practice. Kluwer Academic/Plenum Publishers, New York, pp 317–338CrossRefGoogle Scholar
  172. Heuser A, Mecklenburg L, Ockert D, Kohler M, Kemkowski J (2013) Selective inhibition of PDE4 in Wistar rats can lead to dilatation in testis, efferent ducts, and epididymis and subsequent formation of sperm granulomas. Toxicol Pathol 41(4):615–627.  https://doi.org/10.1177/0192623312463783. Epub 2012 Nov 29. PubMed PMID: 23197197CrossRefPubMedPubMedCentralGoogle Scholar
  173. Heywood R, Wadsworth PF (1981) The experimental toxicology of estrogens. In: Chaudhury RR (ed) Pharmacology of estrogens. International encyclopedia of pharmacology and therapeutics, Section 106. Pergamon Press, New York, pp 63–80Google Scholar
  174. Highman B, Norvell MJ, Shellenberger TE (1978) Pathological changes in female C3H mice continuously fed diets containing diethylstilbestrol or 17beta-estradiol. J Environ Pathol Toxicol 1:1–30PubMedPubMedCentralGoogle Scholar
  175. Hikim AP, Leung A, Swerdloff RS (1995) Involvement of apoptosis in the induction of germ cell degeneration in adult rat after gonadotropin-releasing hormone antagonist treatment. Endocrinology 136:2770–2775. PMID: 7750502PubMedCrossRefPubMedCentralGoogle Scholar
  176. Hilbe M, Jaros P, Ehrensperger F, Zlinszky K, Janett F, Hässig M, Thun R (2006) Histomorphological and immunohistochemical findings in testes, bulbourethral glands and brain of immunologically castrated male piglets. Schweiz Arch Tierheilkd 148(11):599–608PubMedCrossRefPubMedCentralGoogle Scholar
  177. Hild SA, Reel JR, Dykstra MJ, Mann PC, Marshall GR (2007) Acute adverse effects of the indenopyridine CDB- 4022 on the ultrastructure of Sertoli cells, spermatocytes, and spermatids in rat testes: comparison to the known Sertoli cell toxicant Di-n-pentylphthalate (DPP). J Androl 28:621–629.  https://doi.org/10.2164/jandrol.106.002295. PMID: 17409460CrossRefPubMedPubMedCentralGoogle Scholar
  178. Hooser SB, Douds DP, DeMerell DG, Hoyer PB, Sipes IG (1994) Long-term ovarian and gonadotropin changes in mice exposed to 4-vinylcyclohexene. Reprod Toxicol 8:315–323PubMedCrossRefPubMedCentralGoogle Scholar
  179. Hovey RC, Aimo L (2010) Diverse and active roles for adipocytes during mammary gland growth and function. J Mammary Gland Biol Neoplasia 15:279–290PubMedPubMedCentralCrossRefGoogle Scholar
  180. Hovey RC, McFadden TB, Akers RM (1999) Regulation of mammary gland growth and morphogenesis by the mammary fat pad: a species comparison. J Mammary Gland Biol Neoplasia 4:53–68PubMedCrossRefPubMedCentralGoogle Scholar
  181. Hovey RC, Trott JF, Vonderhaar BK (2002) Establishing a framework for the functional mammary gland: from endocrinology to morphology. J Mammary Gland Biol Neoplasia 7:17–38PubMedCrossRefPubMedCentralGoogle Scholar
  182. Howroyd PC, Peter B, de Rijk E (2016) Review of sexual maturity in the minipig. Toxicol Pathol 44(4):607–611.  https://doi.org/10.1177/0192623316642881. Epub 2016 Apr 21. Review. PubMed PMID: 27102651CrossRefPubMedPubMedCentralGoogle Scholar
  183. Hoyer PB (2004) Ovarian toxicity in small pre-antral follicles. In: Hoyer PB (ed) Ovarian toxicology. CRC Press, Boca Raton, pp 17–40CrossRefGoogle Scholar
  184. Huseby RA (1980) Demonstration of a direct carcinogenic effect of estradiol on Leydig cells of the mouse. Cancer Res 40:1006–1013PubMedPubMedCentralGoogle Scholar
  185. Hvid H, Thorup I, Oleksiewicz MB, Sjögren I, Jensen HE (2011) An alternative method for preparation of tissue sections from the rat mammary gland. Exp Toxicol Pathol 63:317–324PubMedCrossRefPubMedCentralGoogle Scholar
  186. ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) (2005) Detection of toxicity to reproduction for medicinal products & toxicity to male fertility S5(R2). http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S5/Step4/S5_R2__Guideline.pdf. Accessed 12 Feb 2017
  187. ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) (2009) Guidance on nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals M3(R2). http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Multidisciplinary/M3_R2/Step4/M3_R2__Guideline.pdf. Accessed 12 Feb 2017
  188. ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) (2011) Preclinical safety evaluation of biotechnology-derived pharmaceuticals S6(R1). http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S6_R1/Step4/S6_R1_Guideline.pdf. Accessed 12 Feb 2017
  189. Iguchi T, Takasugi N, Bern HA, Mills KT (1986) Frequent occurrence of polyovular follicles in ovaries of mice exposed neonatally to diethylstilbestrol. Teratology 34:29–35PubMedCrossRefPubMedCentralGoogle Scholar
  190. Iguchi T, Todoroki R, Takasugi N, Petrow Y (1988) The effects of an aromatase inhibitor and a 5 alpha-reductase inhibitor upon the occurrence of polyovular follicles, persistent anovulation, and permanent vaginal stratification in mice treated neonatally with testosterone. Biol Reprod 39:689–697PubMedCrossRefPubMedCentralGoogle Scholar
  191. Ilha MR, Newman SJ, van Amstel S, Fecteau KA, Rohrbach BW (2010) Uterine lesions in 32 female miniature pet pigs. Vet Pathol 47(6):1071–1075.  https://doi.org/10.1177/0300985810382522. Epub 2010 Sep 3. PubMed PMID: 20817893CrossRefPubMedPubMedCentralGoogle Scholar
  192. Ilio KY, Hess RA (1994) Structure and function of the ductuli efferentes: a review. Microsc Res Techn 29:432–467CrossRefGoogle Scholar
  193. Imagawa W, Bandyopadhyay GK, Nandi S (1990) Regulation of mammary epithelial cell growth in mice and rats. Endocr Rev 11:494–523PubMedCrossRefPubMedCentralGoogle Scholar
  194. Imagawa W, Pedchenko VK, Helber J, Zhang H (2002) Hormone/growth factor interactions mediating epithelial/stromal communication in mammary gland development and carcinogenesis. J Steroid Biochem Mol Biol 80:213–230PubMedCrossRefPubMedCentralGoogle Scholar
  195. Ishii S, Ube M, Okada M et al (2009) Collaborative work on evaluation of ovarian toxicity. 17. Two- or four-week repeated-dose studies and fertility study of sulpiride in female rats. J Toxicol Sci 34:SP175–SP188PubMedCrossRefPubMedCentralGoogle Scholar
  196. Jabara AG (1962) Some tissue changes in the dog following stilboestrol administration. Aust J Exp Biol Med Sci 40:293–308PubMedCrossRefPubMedCentralGoogle Scholar
  197. Jack D, Poynter D, Spurling NW (1983) Beta-adrenoceptor stimulants and mesovarian leiomyomas in the rat. Toxicology 27:315–320PubMedCrossRefPubMedCentralGoogle Scholar
  198. Jahnukainen K, Chrysis D, Hou M, Parvinen M, Eksborg S, Söder O (2004) Increased apoptosis occurring during the first wave of spermatogenesis is stage-specific and primarily affects midpachytene spermatocytes in the rat testis. Biol Reprod 70:290–296PubMedCrossRefPubMedCentralGoogle Scholar
  199. James RW, Heywood R (1979) Age-related variations in the testes and prostate of beagle dogs. Toxicology 12:273–279PubMedCrossRefPubMedCentralGoogle Scholar
  200. Jefferson WN, Padilla-Banks E, Newbold RR (2007) Disruption of the developing female reproductive system by phytoestrogens: genistein as an example. Mol Nutr Food Res 51:832–844PubMedCrossRefPubMedCentralGoogle Scholar
  201. Ji F, Hurley WL, Kim SW (2006 Mar) Characterization of mammary gland development in pregnant gilts. J Anim Sci 84(3):579–587PubMedCrossRefPubMedCentralGoogle Scholar
  202. Jöchle W, Andersen AC (1977) The estrus cycle in the dog: a review. Theriogenology 7:113–140PubMedCrossRefPubMedCentralGoogle Scholar
  203. Johnson AN (1989) Comparative aspects of contraceptive steroids – effects observed in beagle dogs. Toxicol Pathol 17:389–395PubMedCrossRefPubMedCentralGoogle Scholar
  204. Johnson KJ (2014) Testicular histopathology associated with disruption of the Sertoli cell cytoskeleton. Spermatogenesis 4(2):e979106PubMedCrossRefPubMedCentralGoogle Scholar
  205. Johnston SD, Root Kustritz MV, Olson PN (2001) The canine estrus cycle. In: Canine and feline theriogenology. Saunders, Philadelphia, pp 16–31Google Scholar
  206. Junaid M, Chowdhuri DK, Narayan R, Shanker R, Saxena DK (1997) Lead-induced changes in ovarian follicular development and maturation in mice. J Toxicol Environ Health 50:31–40PubMedCrossRefPubMedCentralGoogle Scholar
  207. Juniewicz PE, Oesterling JE, Walters JR, Steele RE, Niswender GD, Coffee DS, Ewing LL (1988) Aromatase inhibition in the dog. I. Effect on serum LH, serum testosterone concentrations, testicular secretions and spermatogenesis. J Urol 139:827–831PubMedCrossRefPubMedCentralGoogle Scholar
  208. Junker-Walker U, Nogues V (1994) Changes induced by treatment with aromatase inhibitors in testicular Leydig cells of rats and dogs. Exp Toxicol Pathol 46:211–213PubMedCrossRefPubMedCentralGoogle Scholar
  209. Kafali H, Iriadam M, Ozardah I, Demir N (2004) Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. Arch Med Res 35:103–108PubMedCrossRefPubMedCentralGoogle Scholar
  210. Kangawa A, Masayoshi O, Enya S, Yoshida T, Kangawa Y, Shibata M (2016) Spermatogenesis in the microminipig. Toxicol Pathol 44:974–986PubMedCrossRefPubMedCentralGoogle Scholar
  211. Kaplan JR, Chen H, Appt SE, Lees CJ, Franke AA, Berga SL, Wilson ME, Manuck SB, Clarkson TB (2010) Impairment of ovarian function and associated health-related abnormalities are attributable to low social status in premenopausal monkeys and not mitigated by a high-isoflavone soy diet. Hum Reprod 25:3083–3094PubMedPubMedCentralCrossRefGoogle Scholar
  212. Karlsson S, Iatropoulos MJ, Williams GM, Kangas L, Nieminen L (1998) The proliferation in uterine compartments of intact rats of two different strains exposed to high doses of tamoxifen or toremifene. Toxicol Pathol 26:759–768PubMedCrossRefPubMedCentralGoogle Scholar
  213. Kawakami E, Tsutsui T, Ogasa A (1991) Histological observations of the reproductive organs of the male dog from birth to sexual maturity. J Vet Med Sci 53:241–248PubMedCrossRefPubMedCentralGoogle Scholar
  214. Keane KA, Parker GA, Regan KS, Picut C, Dixon D, Creasy D, Giri D, Hukkanen RR (2015) Scientific and regulatory policy committee (SRPC) points to consider: histopathology evaluation of the pubertal development and thyroid function assay (OPPTS 890.1450, OPPTS 890.1500) in rats to screen for endocrine disruptors. Toxicol Pathol 43:1047–1063PubMedPubMedCentralCrossRefGoogle Scholar
  215. Keeney DS, Mendis-Handagama SM, Zirkin BR, Ewing LL (1988) Effect of long term deprivation of luteinizing hormone on Leydig cell volume, Leydig cell number, and steroidogenic capacity of the rat testis. Endocrinology 12:2906–2915CrossRefGoogle Scholar
  216. Kennel P, Pallen C, Barale-Thomas E, Espuña G, Bars R (2003) Tamoxifen: 28-day oral toxicity study in the rat based on the Enhanced OECD Test Guideline 407 to detect endocrine effects. Arch Toxicol 77:487–499PubMedCrossRefPubMedCentralGoogle Scholar
  217. Kerr JB, Millar M, Maddocks S, Sharpe RM (1993) Stage-dependent changes in spermatogenesis and Sertoli cells in relation to onset of spermatogenic failure following withdrawal of testosterone. Anat Rec 235:547–559PubMedCrossRefPubMedCentralGoogle Scholar
  218. Kim J, Sato M, Li Q et al (2008) Peroxisome proliferator-activated receptor gamma is a target of progesterone regulation in the preovulatory follicles and controls ovulation in mice. Mol Cell Biol 28:1770–1782PubMedPubMedCentralCrossRefGoogle Scholar
  219. Kim HS, Kang SC, Zhang HS, Kang JS, Kim JH, Kim KH, Kang BH, Yoon BI (2010) Uterine adenomyosis in beagle dogs. Lab Anim Res 26:211–213CrossRefGoogle Scholar
  220. King A, Burrows T, Loke YW (1996) Human uterine natural killer cells. Nat Immun 15:41–52PubMedPubMedCentralGoogle Scholar
  221. Kirigaya A, Kim H, Hayashi S, Chambon P, Watanabe H, Iguchi T, Sato T (2009) Involvement of estrogen receptor beta in the induction of polyovular follicles in mouse ovaries exposed neonatally to. Zool Sci 26:704–712PubMedCrossRefPubMedCentralGoogle Scholar
  222. Kleinberg DL (1998) Role of IGF-I in normal mammary development. Breast Cancer Res 47:201–208CrossRefGoogle Scholar
  223. Kozlosky JC, Mysore J, Clark SP, Burr NH, Li J, Aranibar N, Vuppugalla R, West RC, Mangipudy RS, Grazian MJ (2015) Comparison of physiologic and pharmacologic parameters in Asian and mauritius cynomolgus monkeys. Regul Toxicol Pharmacol 73:27–42PubMedCrossRefPubMedCentralGoogle Scholar
  224. Ku WW, Pagliusi F, Foley G, Roesler A, Zimmerman T (2010) A simple orchidometric method for the preliminary assessment of maturity status in male cynomolgus monkeys (Macaca fascicularis) used for nonclinical safety studies. J Pharmacol Toxicol Methods 61(1):32–37.  https://doi.org/10.1016/j.vascn.2009.10.006. Epub 2009 Nov 10. PubMed PMID: 19903535CrossRefPubMedPubMedCentralGoogle Scholar
  225. Kumar TR, Wang Y, Lu N, Matzuk MM (1997) Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet 15:201–204PubMedCrossRefPubMedCentralGoogle Scholar
  226. Kumasaka T, Itoh E, Watanabe H et al (1994) Effects of various forms of progestin on the endometrium of the estrogen-primed, ovariectomized rat. Endocr J 41:161–169PubMedCrossRefPubMedCentralGoogle Scholar
  227. Kumazawa T, Nakajima A, Ishiguro T et al (2009) Collaborative work on evaluation of ovarian toxicity. 15. Two- or four-week repeated-dose studies and fertility study of bromocriptine in female rats. J Toxicol Sci 34:SP157–SP165PubMedCrossRefPubMedCentralGoogle Scholar
  228. La DK, Creasy DM, Hess RA, Baxter E, Pereira ME, Johnson CA, Vinken P, Snook SS (2012) Efferent duct toxicity with secondary testicular changes in rats following administration of a novel leukotriene A4 hydrolase inhibitor. Toxicol Pathol 40:705–714PubMedCrossRefPubMedCentralGoogle Scholar
  229. Laffan SB, Posobiec LM, Uhl JE, Vidal JD (2018) Species comparison of postnatal development of the female reproductive system. Birth Defects Res 110(3):163–189.  https://doi.org/10.1002/bdr2.1132. Epub 2017 Dec 15. Review. PubMed PMID: 29243395CrossRefPubMedPubMedCentralGoogle Scholar
  230. Laqueur GL, Fluhmann CF (1942) Effects of testosterone propionate in immature and adult female rats. Endocrinology 30:93–101CrossRefGoogle Scholar
  231. Latendresse JR, Warbrittion AR, Jonassen H, Creasy DM (2002) Fixation of testes and eyes using a modified Davidson’s fluid: comparison with Bouin’s fluid and conventional Davidson’s fluid. Toxicol Pathol 30(4):524–533. PubMed PMID: 12187944PubMedPubMedCentralCrossRefGoogle Scholar
  232. Latendresse JR, Bucci TJ, Olson G et al (2009) Genistein and ethinyl estradiol dietary exposure in multigenerational and chronic studies induce similar proliferative lesions in mammary gland of male Sprague-Dawley rats. Reprod Toxicol 28:342–353PubMedCrossRefPubMedCentralGoogle Scholar
  233. Leblond CP, Clermont Y (1952) Definition of the stages of the cycle of the seminiferous epithelium in the rat. Ann N Y Acad Sci 55:548–573PubMedCrossRefPubMedCentralGoogle Scholar
  234. Lederman MA, Lebesgue D, Gonzalez VV et al (2010) Age-related LH surge dysfunction correlates with reduced responsiveness of hypothalamic anteroventral periventricular nucleus kisspeptin neurons to estradiol positive feedback in middle-aged rats. Neuropharmacology 58:314–320PubMedCrossRefPubMedCentralGoogle Scholar
  235. Lee VW, de Kretser DM, Hudson B, Wang C (1975) Variations in serum FSH, LH and testosterone levels in male rats from birth to sexual maturity. J Reprod Fertil 42:121–126PubMedCrossRefPubMedCentralGoogle Scholar
  236. Lee J-H, Sugimura M, Kudo N (1976) Segmentation of the rat oviduct. Jpn J Vet Res 24:77–86PubMedPubMedCentralGoogle Scholar
  237. Lee K-P, Frame SR, Sykes GP, Valentine R (1993) Testicular degeneration and spermatid retention in young male rats. Toxicol Pathol 21:292–302PubMedCrossRefPubMedCentralGoogle Scholar
  238. Lee J, Richburg JH, Younkin SC, Boekelheide K (1997) The Fas system is a key regulator of germ cell apoptosis in the testis. Endocrinology 138:2081–2088PubMedCrossRefPubMedCentralGoogle Scholar
  239. Lefevre J, McClintock MK (1988) Reproductive senescence in female rats: a longitudinal study of individual differences in estrous cycles and behavior. Biol Reprod 38:780–789PubMedCrossRefPubMedCentralGoogle Scholar
  240. LeFevre J, McClintock MK (1991) Isolation accelerates reproductive senescence and alters its predictors in female rats. Horm Behav 25:258–272PubMedCrossRefPubMedCentralGoogle Scholar
  241. Lefèvre CM, Sharp JA, Nicholas KR (2010) Evolution of lactation: ancient origin and extreme adaptation of the lactation system. Annu Rev Genomics Hum Genet 11:219–238PubMedCrossRefPubMedCentralGoogle Scholar
  242. Lewis DJ (1987) Ovarian neoplasia in the Sprague-Dawley rat. Environ Health Perspect 73:77–90PubMedPubMedCentralCrossRefGoogle Scholar
  243. Lewis EM, Barnett JF Jr, Freshwater L, Hoberman AM, Christian MS (2002 Nov) Sexual maturation data for Crl Sprague-Dawley rats: criteria and confounding factors. Drug Chem Toxicol 25(4):437–458. Review. PubMed PMID: 12378951Google Scholar
  244. Lezmi S, Thibault-Duprey K, Bidaut A et al (2010) Spontaneous metritis related to the presence of vaginal septum in pregnant Sprague Dawley Crl:CD(SD) rats: impact on reproductive toxicity studies. Vet Pathol 48:964.  https://doi.org/10.1177/0300985810391113CrossRefPubMedPubMedCentralGoogle Scholar
  245. Li S, Davis B (2007) Evaluating rodent vaginal and uterine histology in toxicity studies. Birth Defects Res B Dev Reprod Toxicol 80:246–252PubMedCrossRefPubMedCentralGoogle Scholar
  246. Lipschutz A, Iglesias R, Panasevich VI, Salinas S (1967) Pathological changes induced in the uterus of mice with the prolonged administration of progesterone and 19-nor-contraceptives. Br J Cancer 21:160–165PubMedPubMedCentralCrossRefGoogle Scholar
  247. Long GG (2002) Apparent mesonephric duct (rete anlage) origin for cysts and proliferative epithelial lesions in the mouse ovary. Toxicol Pathol 30:592–598PubMedCrossRefPubMedCentralGoogle Scholar
  248. Losco PE, Leach MW, Sinha D, Davis P, Schmahai TJ, Nomier A, Kakkaar T, Reyderman L, Lynch ME (2007) Administration of an antagonist of neurokinin receptors 1, 2 and 3 results in reproductive tract changes in beagle dogs, but not rats. Toxicol Pathol 35:310–322PubMedCrossRefPubMedCentralGoogle Scholar
  249. Lotz W, Krause R (1978) Correlation between the effects of neuroleptics on prolactin release, mammary stimulation and the vaginal cycle in rats. J Endocrinol 76:507–515PubMedCrossRefPubMedCentralGoogle Scholar
  250. Lucas JN, Rudmann DG, Credille KM, Irizarry AR, Peter A, Snyder PW (2007) The rat mammary gland: morphologic changes as an indicator of systemic hormonal perturbations induced by xenobiotics. Toxicol Pathol 35:199–207PubMedCrossRefPubMedCentralGoogle Scholar
  251. Luetjens CW, Weinbauer GF (2012) Functional assessment of sexual maturity in male macaques (Macaca fascicularis). Regul Toxicol Pharmacol 63:391–400PubMedCrossRefPubMedCentralGoogle Scholar
  252. Luetjens CM, Weinbauer GF, Wistuba J (2005) Primate spermatogenesis: new insights into comparative testicular organisation, spermatogenic efficiency and endocrine control. Biol Rev Camb Philos Soc 80(3):475–488. Review. PubMed PMID: 16094809PubMedCrossRefPubMedCentralGoogle Scholar
  253. Luo S, Sourla A, Labrie C et al (1998) Effect of twenty-four-week treatment with the antiestrogen EM-800 on estrogen-sensitive parameters in intact and ovariectomized mice. Endocrinology 139:2645–2656PubMedCrossRefPubMedCentralGoogle Scholar
  254. Maekawa A, Maita K (1996) Changes in the uterus and vagina. In: Mohr U, Dungworth DL, Capen CC, Carlton WW, Sundberg JP, Ward JM (eds) Pathobiology of the aging mouse, vol 1. ILSI Press, Washington, DC, pp 469–480Google Scholar
  255. Maffucci JA, Gore AC (2006) Age-related changes in hormones and their receptors in animal models of female reproductive senescence. In: Conn PM (ed) Handbook of models for human aging. Elsevier, San Diego, pp 533–552CrossRefGoogle Scholar
  256. Magoffin DA (2005) Ovarian theca cell. Int J Biochem Cell Biol 37:1344–1349PubMedCrossRefPubMedCentralGoogle Scholar
  257. Majeed SK, Gopinath C (1980) Calcification in the adrenals and ovaries of monkeys. Lab Anim 14:363–365PubMedCrossRefPubMedCentralGoogle Scholar
  258. Mallepell S, Krust A, Chambon P, Brisken C (2006) Paracrine signaling through the epithelial estrogen receptor alpha is required for proliferation and morphogenesis in the mammary gland. Proc Natl Acad Sci U S A 103:2196–2201PubMedPubMedCentralCrossRefGoogle Scholar
  259. Mann PC, Boorman GA, Lollini LO, McMartin DN, Goodman DG (1996) Proliferative lesions of the mammary gland in rats, IS-2. In: Guides for toxicologic pathology. STP/ARP/AFIP, Washington, DCGoogle Scholar
  260. Mäntylä ETE, Karlsson SH, Nieminen LS (1996) Induction of endometrial cancer by tamoxifen in the rat. In: Li JJ, Li SA, Gustafsson JA, Nandi S, Sekely LI (eds) Hormonal carcinogenesis II. Proceedings of the second international symposium. Springer Verlag, New York, pp 442–445CrossRefGoogle Scholar
  261. Markström E, Svensson EC, Shao R, Svangerg B, Billig H (2002) Survival factors regulating ovarian apoptosis – dependence on follicle differentiation. Reproduction 123:23–30PubMedCrossRefPubMedCentralGoogle Scholar
  262. Maronpot RR (1987) Ovarian toxicity and carcinogenicity in eight recent National Toxicology Program studies. Environ Health Perspect 73:125–130. PubMed PMID: 3665857; PubMed Central PMCID: PMC1474570PubMedPubMedCentralCrossRefGoogle Scholar
  263. Masso-Welch PA, Darcy KM, Stangle-Castor NC, Ip MM (2000) A developmental atlas of rat mammary gland histology. J Mammary Gland Biol Neoplasia 5:165–185PubMedCrossRefPubMedCentralGoogle Scholar
  264. Matsuda A, Higuchi K, Karasawa M, Yoneyama S, Deguchi J, Miyamoto M (1997) Fourteen-day oral combination dose toxicity study of CGS 16949 A (aromatase inhibitor) with 5-fluorouracil or tamoxifen in rats. J Toxicol Sci 22:1–24PubMedCrossRefPubMedCentralGoogle Scholar
  265. McDougall K, Hay MA, Goodrowe KL, Gartley CJ, King WA (1997) Changes in the number of follicles and of oocytes in ovaries of prepubertal, peripubertal and mature bitches. J Reprod Fertil Suppl 51:25–31PubMedPubMedCentralGoogle Scholar
  266. McLaren A (1991) Development of the mammalian gonad: the fate of the supporting cell lineage. BioEssays 13:151–156PubMedCrossRefPubMedCentralGoogle Scholar
  267. McMullen ML, Cho BN, Yates CJ, Mayo KE (2001) Gonadal pathologies in transgenic mice expressing the rat inhibin alpha-subunit. Endocrinology 142:5005–5014PubMedCrossRefPubMedCentralGoogle Scholar
  268. McShane TM, Wise PM (1996) Life-long moderate caloric restriction prolongs reproductive life span in rats without interrupting estrous cyclicity: effects on the gonadotropin-releasing hormone/luteinizing hormone axis. Biol Reprod 54:70–75PubMedCrossRefPubMedCentralGoogle Scholar
  269. Medina D (1982) Mammary tumors. In: Foster HL, Small JD, Fox JG (eds) The mouse in biomedical research. Volume IV. Experimental biology and oncology. Academic Press, New York, pp 373–396Google Scholar
  270. Medina D (2008) Premalignant and malignant mammary lesions induced by MMTV and chemical carcinogens. J Mammary Gland Biol Neoplasia 13:271–277PubMedCrossRefPubMedCentralGoogle Scholar
  271. Meistrich ML (1986) Components of testicular function and sensitivity to disruption. Biol Reprod 34:17–28PubMedCrossRefPubMedCentralGoogle Scholar
  272. Meistrich ML (2013) Effects of chemotherapy and radiotherapy on spermatogenesis in humans. Fertil Steril 100(5):1180–1186.  https://doi.org/10.1016/j.fertnstert.2013.08.010. Epub 2013 Sep 4. Review. PubMed PMID: 24012199; PubMed Central PMCID: PMC3826884CrossRefPubMedPubMedCentralGoogle Scholar
  273. Meistrich ML, Shetty G (2003) Inhibition of spermatogonial differentiation by testosterone. J Androl 24(2):135–148. Review. PubMed PMID: 12634296PubMedCrossRefPubMedCentralGoogle Scholar
  274. Meistrich ML, Wilson G, Huhtaniemi I (1999) Hormonal treatment after cytotoxic therapy stimulates recovery of spermatogenesis. Cancer Res 59(15):3557–3560. PubMed PMID: 10446960PubMedPubMedCentralGoogle Scholar
  275. Meistrich ML, Wilson G, Porter KL, Huhtaniemi I, Shetty G, Shuttlesworth GA (2003) Restoration of spermatogenesis in dibromochloropropane (DBCP)-treated rats by hormone suppression. Toxicol Sci 76(2):418–426PubMedCrossRefPubMedCentralGoogle Scholar
  276. Merry BJ, Holehan AM (1979) Onset of puberty and duration of fertility in rats fed a restricted diet. J Reprod Fertil 57:253–259PubMedCrossRefPubMedCentralGoogle Scholar
  277. Messinis IE, Messini CI, Dafopoulos K (2010) The role of gonadotropins in the follicular phase. Ann N Y Acad Sci 1205:5–11PubMedCrossRefPubMedCentralGoogle Scholar
  278. Mialot JP, Thibier M, Toublanc JE, Castanier M, Scholler R (1988) Plasma concentration of luteinizing hormone, testosterone, dehydroepiandrosterone, androstenedione between birth and one year in the male dog: longitudinal study and hCG stimulation. Andrologia 20:145–154PubMedCrossRefPubMedCentralGoogle Scholar
  279. Mitchard TL, Klein S (2016 Feb–Mar) Reproductive senescence, fertility and reproductive tumour profile in ageing female Han Wistar rats. Exp Toxicol Pathol 68(2–3):143–147.  https://doi.org/10.1016/j.etp.2015.11.006. Epub 2015 Dec 4. PubMed PMID: 26655996
  280. Mirsky ML, Sivaraman L, Houle C, Potter DM, Chapin RE, Cappon GD (2011) Histologic and cytologic detection of endocrine and reproductive tract effects of exemestane in female rats treated for up to twenty-eight days. Toxicol Pathol 39:589–605PubMedCrossRefPubMedCentralGoogle Scholar
  281. Misdorp W (2002) Tumors of the mammary gland. In: Meuten DJ (ed) Tumors in domestic animals, 4th edn. Iowa State Press, Ames, pp 575–606Google Scholar
  282. Misdorp W, Else RW, Hellmén E, Lipscomb TP (1999) Histological classification of mammary tumors of the dog and the cat, 2nd series, vol VII. AFIP, Washington, DC, pp 1–59Google Scholar
  283. Mody JK (1963) Structural changes in the ovaries of IF mice due to age and various other states: demonstration of spontaneous pseudopregnancy in grouped virgins. Anat Rec 145:439–447.  https://doi.org/10.1002/ar.1091450307CrossRefGoogle Scholar
  284. Moffitt JS, Bryant BH, Hall SJ, Boekelheide K (2007) Dose-dependent effects of Sertoli cell toxicants 2,5-hexanedione, carbendazim, and mono-(2-ethylhexyl) phthalate in adult rat testis. Toxicol Pathol 35:719–727.  https://doi.org/10.1080/01926230701481931. PMID: 17763286CrossRefGoogle Scholar
  285. Mohr U (1993) Integumentary system. In: Mohr U (ed) International classification of rodent tumors: Part I: The rat. International Agency for Research on Cancer, LyonsGoogle Scholar
  286. Molenaar R, de Rooij DG, Rommerts FF, van der Molen HJ (1986) Repopulation of Leydig cells in mature rats after selective destruction of the existent Leydig cells with ethylene dimethane sulfonate is dependent on luteinizing hormone and not follicle-stimulating hormone. Endocrinology 118:2546–2554PubMedCrossRefPubMedCentralGoogle Scholar
  287. Morales A, Mohamed F, Cavicchia JC (2007) Apoptosis and blood-testis barrier during the first spermatogenic wave in the pubertal rat. Anat Rec 290:206–214CrossRefGoogle Scholar
  288. Mori T, Singtripop T, Kawashima S (1991) Animal model of uterine adenomyosis: is prolactin a potent inducer of adenomyosis in mice? Am J Obstet Gynecol 165:232–234PubMedCrossRefPubMedCentralGoogle Scholar
  289. Mossman HW, Duke KL (1973) Comparative morphology of the mammalian ovary. University of Wisconsin Press, MadisonGoogle Scholar
  290. Murakoshi M, Ikeda R, Tagawa M, Iwasaka T, Nakayama T (2000) Histopathological study of female beagle dogs for four year treatment with subcutaneous implantation of chlormadinone actetate (CMA). Tokai J Exp Clin Med 25:87–91PubMedPubMedCentralGoogle Scholar
  291. Nakai M, Hess RA, Moore BJ, Guttroff RF, Strader LF, Linder RE (1992) Acute and long-term effects of a single dose of the fungicide carbendazim (methyl 2-benzimidazole carbamate) on the male reproductive system in the rat. J Androl 13:507–518PubMedPubMedCentralGoogle Scholar
  292. Nandi S (1958) Endocrine control of mammary-gland development and function in the C3H/he Crgl mouse. J Natl Cancer Inst 21:1039–1063PubMedPubMedCentralGoogle Scholar
  293. Nass TE, LaPolt PS, Judd HL, Lu JKH (1984) Alterations in ovarian steroid and gonadotrophin secretion preceding the cessation of regular oestrous cycles in ageing female rats. J Endocrinol 100:43–50PubMedCrossRefPubMedCentralGoogle Scholar
  294. Naylor MJ, Ormandy CJ (2002) Mouse strain-specific patterns of mammary epithelial ductal side branching are elicited by stromal factors. Dev Dyn 225:100–105PubMedCrossRefPubMedCentralGoogle Scholar
  295. Neal-Perry G, Santoro NF (2006) Aging in the hypothalamic-pituitary-ovarian axis. In: Neill JD (ed) Knobil and Neill’s physiology of reproduction, 3rd edn. Elsevier, San Diego, pp 2729–2755CrossRefGoogle Scholar
  296. Nelson LW, Kelly WA (1974) Changes in canine mammary gland histology during the estrous cycle. Toxicol Appl Pharmacol 27:113–122PubMedCrossRefPubMedCentralGoogle Scholar
  297. Nelson JF, Felicio LS, Osterburg HH, Finch CE (1981) Altered profiles of estradiol and progesterone associated with prolonged estrous cycles and persistent vaginal cornification in aging C578L/6J mice. Biol Reprod 24:784–794PubMedCrossRefPubMedCentralGoogle Scholar
  298. Nelson JF, Felicio LS, Randall PK, Sims C, Finch CE (1982) A longitudinal study of estrous cyclicity in aging C57BL/6J mice: I. Cycle frequency, length and vaginal cytology. Biol Reprod 27(2):327–339. PubMed PMID: 6889895PubMedCrossRefPubMedCentralGoogle Scholar
  299. Nelson JF, Karelus K, Felicio LS, Johnson TE (1990) Genetic influences on the timing of puberty in mice. Biol Reprod 42(4):649–655. PubMed PMID: 2346773PubMedCrossRefPubMedCentralGoogle Scholar
  300. Nephew KP, Osborne E, Lubet RA, Grubbs CJ, Khan SA (2000) Effects of oral administration of tamoxifen, toremifene, dehydroepiandrosterone, and vorozole on uterine histomorphology in the rat. Proc Soc Exp Biol Med 223:288–294PubMedCrossRefPubMedCentralGoogle Scholar
  301. Neville MC (2005) Lactation and its hormonal control. In: Neill JD (ed) Knobil and Neill’s physiology of reproduction, vol 2, 3rd edn. Elsevier, St. Louis, pp 2993–3054Google Scholar
  302. Neville MC, McFadden TB, Forsyth I (2002) Hormonal regulation of mammary differentiation and milk secretion. J Mammary Gland Biol Neoplasia 7:49–66PubMedCrossRefPubMedCentralGoogle Scholar
  303. Ng ST, Zhou J, Adesanya OO, Wang J, LeRoith D, Bondy CA (1997) Growth hormone treatment induces mammary gland hyperplasia in aging primates. Nat Med 3:1141–1144PubMedCrossRefPubMedCentralGoogle Scholar
  304. Niehoff MO, Bergmann M, Weinbauer GF (2010) Effects of social housing of sexually mature male cynomolgus monkeys during general and reproductive toxicity evaluation. Reprod Toxicol 29:57–67PubMedCrossRefPubMedCentralGoogle Scholar
  305. Nishiyama S, Okudaira M, Saito N (2006) Mechanisms of rolipram-induced increase in the incidence of mammary adenocarcinoma: histopathological study of a 104-week oral carcinogenicity study in female Sprague-Dawley rats. Arch Toxicol 80(2):88–97. Epub 2005 Sep 16. PubMed PMID: 16167140PubMedCrossRefPubMedCentralGoogle Scholar
  306. Noden DM, De Lahunta A (1985) Embryology of domestic animals. Williams and Wilkins, BaltimoreGoogle Scholar
  307. Noritake K-I, Suzuki J, Matsuoka T, Makino T, Ohnishi H, Shimomura K, Uenoyama Y, Tsukamura H, Maeda K-I, Sanbuissho A (2011) Testicular toxicity induced by a triple neurokinin receptor antagonist in male dogs. Reprod Toxicol 31:440–446.  https://doi.org/10.1016/j.reprotox.2010.12.007. PMID: 21185367CrossRefPubMedPubMedCentralGoogle Scholar
  308. Nozaki Y, Furubo E, Matsuno T et al (2009) Collaborative work on evaluation of ovarian toxicity. 6. Two- or four-week repeated-dose studies and fertility study of cisplatin in female rats. J Toxicol Sci 34:73–81CrossRefGoogle Scholar
  309. O’Connor JC, Plowchalk DR, Van Pelt CS, Davis LG, Cook JC (2000) Role of prolactin in chloro-S-triazine rat mammary tumorigenesis. Drug Chem Toxicol 23:575–601PubMedCrossRefPubMedCentralGoogle Scholar
  310. O’Connor JC, Cook JC, Marty MS, Davis LG, Kaplan AM, Carney EW (2002) Evaluation of Tier 1 screening approaches for detecting endocrine-active compounds (EACs). Crit Rev Toxicol 32:521–549PubMedCrossRefPubMedCentralGoogle Scholar
  311. O’Donnell L (2014) Mechanisms of spermiogenesis and spermiation and how they are disturbed. Spermatogenesis 4(2):e979623PubMedCrossRefPubMedCentralGoogle Scholar
  312. Oakberg E (1956) A description of spermiogenesis in the mouse, and its use in the analysis of the cycle of the seminiferous epithelium and germ cell renewal. Am J Anat 99:391–413PubMedCrossRefPubMedCentralGoogle Scholar
  313. Obasanjo IO, Cline JM, Schmotzer S, Weaver DS (1998) Nandrolone decanoate causes pathologic changes in the uterus of surgically postmenopausal female cynomolgus macaques. Menopause 5:163–168PubMedPubMedCentralGoogle Scholar
  314. Ohta Y, Sato T, Iguchi T (1993) Immunocytochemical localization of progesterone receptor in the reproductive tract of adult female rats. Biol Reprod 48:205–213PubMedCrossRefPubMedCentralGoogle Scholar
  315. Ohtake S, Fukui M, Hisada S (2009) Collaborative work on evaluation of ovarian toxicity. 1. Effects of 2- or 4-week repeated-dose administration and fertility studies with medroxyprogesterone acetate in female rats. J Toxicol Sci 34 Suppl 1:SP23–SP29PubMedPubMedCentralGoogle Scholar
  316. Oishi Y, Yoshizawa K, Suzuki J et al (1995) Spontaneously occurring mammary adenocarcinoma in a 10-week-old female rat. Toxicol Pathol 23:696–700PubMedCrossRefPubMedCentralGoogle Scholar
  317. Okazaki K, Okazaki S, Nishimura S, Nakamura H, Kitamura Y (2001) A repeated 28-day oral dose toxicity study of methoxychlor in rats, based on the “Enhanced OECD Test Guideline 407” for screening endocrine-disrupting chemicals. Arch Toxicol 75:513–521PubMedCrossRefPubMedCentralGoogle Scholar
  318. Olar TT, Amann RP, Pickett BW (1983) Relationships among testicular size, daily production and output of spermatozoa, and extragonadal spermatozoal reserves of the dog. Biol Reprod 29(5):1114–1120. PubMed PMID: 6652178PubMedCrossRefPubMedCentralGoogle Scholar
  319. Orth JM (1982) Proliferation of Sertoli cells in fetal and postnatal rats: a quantitative autoradiographic study. Anat Rec 203:485–492PubMedCrossRefPubMedCentralGoogle Scholar
  320. O’Shea JD (1981) Structure-function relationships in the wall of the ovarian follicle. Aust J Biol Sci 34:379–394PubMedCrossRefPubMedCentralGoogle Scholar
  321. Osmun P (1985) Rate and course of atresia during follicular development in the adult cyclic rat. J Reprod Fertil 73:261–270CrossRefGoogle Scholar
  322. Ota H, Wakizaka A, Fukushima M (1986) Modulation of ovarian LH receptor and serum hormone levels in rats with hyperprolactinemia induced by administration of ovine prolactin or sulpiride. Tohoku J Exp Med 148:213–227PubMedCrossRefPubMedCentralGoogle Scholar
  323. Pady TJ, McComb RD, Shull JD (1999) Estrogen action in the regulation of cell proliferation, cell survival, and tumorigenesis in the rat anterior pituitary gland. Endocrine 11:217–233CrossRefGoogle Scholar
  324. Paltiel HJ, Diamond DA, Di Canzio J, Zurakowski D, Borer JG, Atala A (2002) Testicular volume: comparison of orchidometer and US measurements in dogs. Radiology 222(1):114–119. PubMed PMID: 11756714PubMedCrossRefPubMedCentralGoogle Scholar
  325. Parmar H, Cunha GR (2004) Epithelial-stromal interactions in the mouse and human mammary gland in vivo. Endocr Relat Cancer 11:437–458PubMedCrossRefPubMedCentralGoogle Scholar
  326. Patrick DJ, Rebelatto MC (2015) Toxicologic pathology and background lesions of nonhuman primates. In: Bluemel J, Korte S, Schenck E, Weinbauer G (eds) The nonhuman primate in nonclinical drug development and safety assessment. Elsevier, London, p 252Google Scholar
  327. Patyna S, Arrigoni C, Terron A, Kim TW, Heward JK, Vonderfecht SL, Denlinger R, Turnquist SE, Evering W (2008) Nonclinical safety evaluation of sunitinib: a potent inhibitor of VEGF, PDGF, KIT, FLT3, and RET receptors. Toxicol Pathol 36:905–916PubMedCrossRefPubMedCentralGoogle Scholar
  328. Payan-Carreira R, Pires MA (2008) Multioocyte follicles in domestic dogs: a survey of frequency of occurrence. Theriogenology 69:977–982PubMedCrossRefPubMedCentralGoogle Scholar
  329. Pelletier G, Labrie C, Labrie F (2000) Localization of oestrogen receptor alpha, oestrogen receptor beta and androgen receptors in the rat reproductive organs. J Endocrinol 165:359–370PubMedCrossRefPubMedCentralGoogle Scholar
  330. Pelliniemi LJ, Fröjdman K, Parank J (1993) Embryological and prenatal Development and function of Sertoli cells. In: Russell LD, Griswold MD (eds) The Sertoli cell. Cache River Press, Clearwater, pp 87–114Google Scholar
  331. Peluso JJ (1992) Morphologic and physiologic features of the ovary. In: Mohr U, Dungworth DL, Capen CC (eds) Pathobiology of the aging rat, vol 1. ILSI Press, Washington, DC, pp 337–349Google Scholar
  332. Peluso JJ, Gordon LR (1992) Nonneoplastic and neoplastic changes in the ovary. In: Mohr U, Dungworth DL, Capen CC (eds) Pathobiology of the aging rat, vol 1. ILSI Press, Washington, DC, pp 351–364Google Scholar
  333. Pepling ME (2006) From primordial germ cell to primordial follicle: mammalian female germ cell development. Genesis 44:622–632PubMedCrossRefPubMedCentralGoogle Scholar
  334. Pereira Bacares ME, Vemireddi V, Creasy D (2017) Testicular fibrous hypoplasia in cynomolgus monkeys (Macaca fascicularis): an incidental, congenital lesion. Toxicol Pathol 45(4):536–543PubMedCrossRefPubMedCentralGoogle Scholar
  335. Pessina MA, Hoyt RF, Goldstein I, Traish AM (2006) Differential regulation of the expression of estrogen, progesterone, and androgen receptors by sex steroid hormones in the vagina: immunohistochemical studies. J Sex Med 3:804–814PubMedCrossRefPubMedCentralGoogle Scholar
  336. Picut CA, Remick AK (2017) Impact of age on the male reproductive system from the pathologist’s perspective. Toxicol Pathol 45:195–205PubMedCrossRefPubMedCentralGoogle Scholar
  337. Picut CA, Swanson CL, Scully KL, Roseman VC, Parker RF, Remick AK (2008) Ovarian follicle counts using proliferating cell nuclear antigen (PCNA) and semi-automated image analysis in rats. Toxicol Pathol 36:674–679PubMedCrossRefPubMedCentralGoogle Scholar
  338. Picut CA, Remick AK, Asakawa MG, Simons ML, Parker GA (2014) Histologic features of prepubertal and pubertal reproductive development in female Sprague-Dawley rats. Toxicol Pathol 42(2):403–413.  https://doi.org/10.1177/0192623313484832. Epub 2013 Apr 18. PubMed PMID: 23599412CrossRefPubMedPubMedCentralGoogle Scholar
  339. Picut CA, Dixon D, Simmons M et al (2015a) Postnatal ovary development in the rat: morphologic study and correlation of morphology to neuroendocrine parameters. Toxicol Pathol 43:343–353PubMedCrossRefPubMedCentralGoogle Scholar
  340. Picut CA, Remick AK, de Rijk EPCT, Simons ML, Stump DG, Parker GA (2015b) Postnatal development of the testis in the rat: morphologic study and correlation of morphology to neuroendocrine parameters. Toxicol Pathol 43:326–342PubMedCrossRefPubMedCentralGoogle Scholar
  341. Picut CA, Ziejewski MK, Stanislaus D (2018) Comparative aspects of pre- and postnatal development of the male reproductive system. Birth Defects Res 110(3):190–227.  https://doi.org/10.1002/bdr2.1133. Epub 2017 Oct 24. Review. PubMed PMID: 29063715CrossRefPubMedPubMedCentralGoogle Scholar
  342. Piner J, Sutherland M, Millar M, Turner K, Newall D, Sharpe RM (2002) Changes in vascular dynamics of the adult rat testis leading to transient accumulation of seminiferous tubule fluid after administration of a novel 5-hydroxytryptamine (5HT) agonist. Reprod Toxicol 16:141–150PubMedCrossRefPubMedCentralGoogle Scholar
  343. Plante I, Stewart MK, Laird DW (2011) Evaluation of mammary gland development and function in mouse models. J Vis Exp (53):e2828.  https://doi.org/10.3791/2828
  344. Plowchalk DR, Mattison DR (1992) Reproductive toxicity of cyclophosphamide in the C57BL/6N mouse: 1. Effects on ovarian structure and function. Reprod Toxicol 6:411–421PubMedCrossRefPubMedCentralGoogle Scholar
  345. Qiu X, Dowling AR, Marino JS et al (2013) Delayed puberty but normal fertility in mice with selective deletion of insulin receptors from Kiss1 cells. Endocrinology 154:1337–1348PubMedPubMedCentralCrossRefGoogle Scholar
  346. Rajah R, Glaser EM, Hirshfield AN (1992) The changing architecture of the neonatal rat ovary during histogenesis. Dev Dyn 194:177–192PubMedCrossRefPubMedCentralGoogle Scholar
  347. Ramaswamy S, Weinbauer GF (2014) Endocrine control of spermatogenesis: role of FSH and LH/testosterone. Spermatogenesis 4(2):e996025PubMedCrossRefPubMedCentralGoogle Scholar
  348. Ramos AMG, Perazzio S, de Camargos AF, Pereira FEL (2005) Spontaneous inflammatory pelvic disease in adult non-castrated female rats treated with estrogen. Braz J Infect Dis 9:6–8PubMedCrossRefPubMedCentralGoogle Scholar
  349. Regan KS, Cline JM, Creasy D et al (2005) STP position paper: ovarian follicular counting in the assessment of rodent reproductive toxicity. Toxicol Pathol 33:409–412PubMedCrossRefPubMedCentralGoogle Scholar
  350. Rehm S (2000) Spontaneous testicular lesions in purpose-bred beagle dogs. Toxicol Pathol 28:782–787PubMedPubMedCentralCrossRefGoogle Scholar
  351. Rehm S, Liebelt AG (1996) Nonneoplastic and neoplastic lesions of the mammary gland. In: Mohr U, Dungworth DL, Capen CC, Carlton WW, Sundberg JP, Ward JM (eds) Pathobiology of the aging mouse, vol 2. ILSI Press, Washington, DC, pp 381–398Google Scholar
  352. Rehm S, Solleveld HA, Portelli ST, Wier PJ (2007a) Histologic changes in ovary, uterus, vagina, and mammary gland of mature beagle dogs treated with the SERM idoxifene. Birth Defects Res B Dev Reprod Toxicol 80:225–232PubMedCrossRefPubMedCentralGoogle Scholar
  353. Rehm S, Stanislaus DJ, Williams AM (2007b) Estrous cycle-dependent histology and review of sex steroid receptor expression in dog reproductive tissues and mammary gland and associated hormone levels. Birth Defects Res B Dev Reprod Toxicol 80:233–245PubMedCrossRefPubMedCentralGoogle Scholar
  354. Rehm S, Stanislaus DJ, Wier PJ (2007c) Identification of drug-induced hyper- or hypoprolactinemia in the female rat based on general and reproductive toxicity study parameters. Birth Defects Res B Dev Reprod Toxicol 80:253–257PubMedCrossRefPubMedCentralGoogle Scholar
  355. Reindel JF, Gough AW, Pilcher GD, Bobrowski WF, Sobocinski GP, de la Iglesia FA (2001) Systemic proliferative changes and clinical signs in cynomolgus monkeys administered a recombinant derivative of human epidermal growth factor. Toxicol Pathol 29:159–173PubMedCrossRefGoogle Scholar
  356. Resko JA, Goy RW, Robinson JA, Norman RL (1982) The pubescent rhesus monkey: some characteristics of the menstrual cycle. Biol Reprod 27:354–361PubMedCrossRefPubMedCentralGoogle Scholar
  357. Rhodes L, Ding VD, Kemp RK, Khan MS, Nakhla AM, Pikounis B, Rosner W, Saunders HM, Feeney WP (2000) Estradiol causes a dose-dependent stimulation of prostate growth in castrated beagle dogs. Prostate 44(1):8–18. PubMed PMID: 10861752PubMedCrossRefPubMedCentralGoogle Scholar
  358. Richert MM, Schwertfeger KL, Ryder JW, Anderson SM (2000) An atlas of mouse mammary gland development. J Mammary Gland Biol Neoplasia 5:227–241PubMedCrossRefPubMedCentralGoogle Scholar
  359. Robaire B, Fan X (1998) Regulation of apoptotic cell death in the rat epididymis. J Reprod Fertil Suppl 53:211–214PubMedPubMedCentralGoogle Scholar
  360. Robinette CL (1988) Sex-hormone-induced inflammation and fibromuscular proliferation in the rat lateral prostate. Prostate 12:271–286PubMedCrossRefPubMedCentralGoogle Scholar
  361. Robinson K, Smith SY, Viau A (2012) Dog juvenile toxicity. In: Hoberman AM, Lewis EM (eds) Pediatric nonclinical drug testing: principles, requirements, and practices. John Wiley & Sons Inc, Hoboken, pp 141–182Google Scholar
  362. Rodgers JB, Sherwood LC, Fink BF, Sadove RC (1993) Estrus detection by using vaginal cytologic examination in miniature swine. Lab Anim Sci 43(6):597–602PubMedPubMedCentralGoogle Scholar
  363. Rodriguez HA, Santambrosio N, Santamaria CG, Muñoz-de-Toro M, Lugue EH (2010) Neonatal exposure to bisphenol A reduces the pool of primordial follicles in the rat ovary. Reprod Toxicol 30:550–557PubMedCrossRefPubMedCentralGoogle Scholar
  364. Roeser HP, Stocks AE, Smith AJ (1978) Testicular damage due to cytotoxic drugs and recovery after cessation of therapy. Aust NZ J Med 8(3):250–254. PubMed PMID: 279319CrossRefGoogle Scholar
  365. Rudmann DG, Cohen IR, Robbins MR, Coutant DE, Henck JW (2005) Androgen dependent mammary gland virilism in rats given the selective estrogen receptor modulator LY2066948 hydrochloride. Toxicol Pathol 33:711–719PubMedCrossRefPubMedCentralGoogle Scholar
  366. Rudmann D, Cardiff R, Chouinard L, Goodman D, Küttler K, Marxfeld H, Molinolo A, Treumann S, Yoshizawa K, INHAND Mammary, Zymbal’s, Preputial, and Clitoral Gland Organ Working Group (2012) Proliferative and nonproliferative lesions of the rat and mouse mammary, Zymbal’s, preputial, and clitoral glands. Toxicol Pathol 40(6 Suppl):7S–39SPubMedCrossRefPubMedCentralGoogle Scholar
  367. Russell LD, Malone JP, Karpas SL (1981) Morphologic pattern elicited by agents affecting spermatogenesis by disruption of its hormonal stimulation. Tissue Cell 13:369–380PubMedCrossRefPubMedCentralGoogle Scholar
  368. Russell LD, Ettlin RA, SinhaHikim AP, Clegg ED (1990) Histological and histopathological evaluation of the testis. Cache River Press, ClearwaterGoogle Scholar
  369. Russo J (2015) Significance of rat mammary tumors for human risk assessment. Toxicol Pathol 43:145–170PubMedCrossRefPubMedCentralGoogle Scholar
  370. Russo IH, Russo J (1994) Aging of the mammary gland. In: Mohr U, Dungworth DL, Capen CC (eds) Pathobiology of the aging rat, vol 2. ILSI Press, Washington, DC, pp 447–458Google Scholar
  371. Russo IH, Tewari M, Russo J (1989a) Morphology and development of the rat mammary gland. In: Jones TC, Mohr U, Hunt RD (eds) Monographs on pathology of laboratory animals. Integument and mammary glands. Springer-Verlag, Berlin, pp 233–252CrossRefGoogle Scholar
  372. Russo J, Russo IH, van Zwieten MJ, Rogers AE, Gusterson BA (1989b) Classification of neoplastic and nonneoplastic lesions of the rat mammary gland. In: Jones TC, Mohr U, Hunt RD (eds) Monographs on pathology of laboratory animals. Integument and mammary glands. Springer-Verlag, Berlin, pp 275–304CrossRefGoogle Scholar
  373. Ryan AM, Eppler DB, Hagler KE, Bruner RH, Thomford PJ, Hall RL, Shopp GM, O’Neill CA (1999) Preclinical safety evaluation of rhuMAbVEGF, an antiangiogenic humanized monoclonal antibody. Toxicol Pathol 27:78–86PubMedCrossRefPubMedCentralGoogle Scholar
  374. Sahara K, Murakoshi M, Nishina T, Kino H, Tsutsui T (1994) Pathologic changes related to subcutaneous implantation of chlormadinone acetate for preventing estrus in bitches. J Vet Med Sci 52:425–427CrossRefGoogle Scholar
  375. Saito K, O’Donnell L, McLachlan I, Robertson DM (2000) Spermiation failure is a major contributor to early spermatogenic suppression caused by hormone withdrawal in adult rats. Endocrinology 141:2779–2785PubMedCrossRefPubMedCentralGoogle Scholar
  376. Sakakura T (1987) Mammary embryogenesis. In: Neville MC, Daniel CW (eds) The mammary gland. Plenum Press, New York, pp 37–66CrossRefGoogle Scholar
  377. Sakamoto H, Saito K, Oohta M, Inoue K, Ogawa Y, Yoshida H (2007) Testicular volume measurement: comparison of ultrasonography, orchidometry, and water displacement. Urology 69(1):152–157. PubMed PMID: 17270639PubMedCrossRefPubMedCentralGoogle Scholar
  378. Sakurada Y, Kudo S, Iwasaki S, Miyata Y, Nishi M, Masumoto Y (2009) Collaborative work on evaluation of ovarian toxicity. 5. Two- or four-week repeated-dose studies and fertility study of busulfan in female rats. J Toxicol Sci 34:65–72CrossRefGoogle Scholar
  379. Samoilov VI, Chebyshev AP (1964) Whole mount preparations of rat and mouse mammary glands. Bull Exp Biol Med 58(6):1468–1469.  https://doi.org/10.1007/BF00792969CrossRefGoogle Scholar
  380. Sanbuissho A, Yoshida M, Hisada S et al (2009) Collaborative work on evaluation of ovarian toxicity by repeated-dose and fertility studies in female rats. J Toxicol Sci 34:SP1–S22PubMedCrossRefPubMedCentralGoogle Scholar
  381. Sánchez-Criado J, Sánchez A, Ruiz A, Gaytán F (1993) Endocrine and morphological features of cystic ovarian condition in antiprogesterone RU486-treated rats. Acta Endocrinol 129:237–245PubMedCrossRefPubMedCentralGoogle Scholar
  382. Sato N, Uchida K, Nakajima M, Watanabe A, Kohira T (2009) Collaborative work on evaluation of ovarian toxicity. 13. Two- or four-week repeated dose studies and fertility study of PPAR alpha/gamma dual agonist in female rats. J Toxicol Sci 34:SP137–SP146PubMedPubMedCentralGoogle Scholar
  383. Sato J, Doi T, Wako Y, Hamamura M, Kanno T, Tsuchitani M, Narama I (2012a) Histopathology of incidental findings in beagles used in toxicity studies. J Toxicol Pathol 25(1):103–134.  https://doi.org/10.1293/tox.25.103. PubMed PMID: 22481862; PubMed Central PMCID: PMC3320160CrossRefPubMedPubMedCentralGoogle Scholar
  384. Sato J, Doi T, Kanno T, Wako Y, Tsuchitani M, Narama I (2012b) Histopathology of incidental findings in cynomolgus monkeys (Macaca fascicularis) used in toxicity studies. J Toxicol Pathol 25:63–101PubMedPubMedCentralCrossRefGoogle Scholar
  385. Sawamoto O, Yamate J, Kuwamura M, Kotani T, Kurisu Z (2003) Development of sperm granulomas in the epididymides of L-cysteine-treated rats. Toxicol Pathol 31:281–289PubMedPubMedCentralGoogle Scholar
  386. Schedin P, Mitrenga T, Kaeck M (2000) Estrous cycle regulation of mammary epithelial cell proliferation, differentiation, and death in the Sprague-Dawley rat: a model for investigating the role of estrous cycling in mammary carcinogenesis. J Mammary Gland Biol Neoplasia 5:211–225PubMedCrossRefPubMedCentralGoogle Scholar
  387. Seachrist DD, Johnson E, Magee C et al (2012) Overexpression of follistatin in the mouse epididymis disrupts fluid resorption and sperm transit in testicular excurrent ducts. Biol Reprod 87(2):41.  https://doi.org/10.1095/biolreprod.111.097527CrossRefPubMedPubMedCentralGoogle Scholar
  388. Seaman WJ (1985) Canine ovarian fibroma associated with prolonged exposure to mibolerone. Toxicol Pathol 13:177–180PubMedCrossRefPubMedCentralGoogle Scholar
  389. Sellers RS, Morton D, Michael B, Roome N, Johnson JK, Yano BL, Perry R, Schafer K (2007) Society of toxicologic pathology position paper: organ weight recommendations for toxicology studies. Toxicol Pathol 35:751–755PubMedCrossRefPubMedCentralGoogle Scholar
  390. Selman PJ, Mol JA, Rutteman GR, van Garderen E (1994) Progestin-induced growth hormone excess in the dog originates in the mammary gland. Endocrinology 134:287–292PubMedCrossRefPubMedCentralGoogle Scholar
  391. Selye H (1940) Effect of chronic progesterone over-dosage on the female accessory sex organs of normal, ovariectomized and hypophysectomized rats. Anat Rec 78:253–271CrossRefGoogle Scholar
  392. Sharpe RM (1994) Regulation of spermatogenesis. In: Knobil E, Neill JD (eds) The physiology of reproduction, 2nd edn. Raven Press, New York, pp 1363–1434Google Scholar
  393. Shetty G, Wilson G, Huhtaniemi I, Shuttlesworth GA, Reissmann T, Meistrich ML (2000) Gonadotropin-releasing hormone analogs stimulate and testosterone inhibits the recovery of spermatogenesis in irradiated rats. Endocrinology 141(5):1735–1745PubMedCrossRefPubMedCentralGoogle Scholar
  394. Shetty G, Wilson G, Hardy MP, Niu E, Huhtaniemi I, Meistrich ML (2002) Inhibition of recovery of spermatogenesis in irradiated rats by different androgens. Endocrinology 143(9):3385–3396. PubMed PMID: 12193551PubMedCrossRefPubMedCentralGoogle Scholar
  395. Shimizu K (2008) Reproductive Hormones and the Ovarian Cycle in Macaques. J Mamm Ova Res 25:122–126CrossRefGoogle Scholar
  396. Shirai M, Sakurai K, Saitoh W et al (2009) Collaborative work on evaluation of ovarian toxicity. 8. Two- or four-week repeated-dose studies and fertility study of Anastrozole in female rats. J Toxicol Sci 34:SP91–SP99PubMedCrossRefPubMedCentralGoogle Scholar
  397. Shirai N, Houle C, Mirsky ML (2015) Using histopathologic evidence to differentiate reproductive senescence from xenobiotic effects in middle-aged female Sprague-Dawley rats. Toxicol Pathol 43:1158–1161PubMedCrossRefPubMedCentralGoogle Scholar
  398. Simpkins JW, Swenberg JA, Weiss N, Brusick D, Eldridge JC, Stevens JT, Handa RJ, Hovey RC, Plant TM, Pastoor TP, Breckenridge CB (2011) Atrazine and breast cancer: a framework assessment of the toxicological and epidemiological evidence. Toxicol Sci 123:441–459PubMedPubMedCentralCrossRefGoogle Scholar
  399. Sleer LS, Taylor CC (2007) Platelet-derived growth factors and receptors in the rat corpus luteum: localization and identification of an effect on luteogenesis. Biol Reprod 76:391–400PubMedCrossRefPubMedCentralGoogle Scholar
  400. Smedley JV, Bailey SA, Perry RW, O’Rourke CM (2002) Methods for predicting sexual maturity in male cynomolgus macaques on the basis of age, body weight, and histologic evaluation of the testes. Contemp Top Lab Anim Sci 41:18–20PubMedPubMedCentralGoogle Scholar
  401. Smith MS, Freeman ME, Neill JD (1975) The control of progesterone secretion during the estrous cycle and early pseudopregnancy in the rat: prolactin, gonadotropin and steroid levels associated with rescue of the corpus luteum of pseudopregnancy. Endocrinology 96:219–226PubMedCrossRefPubMedCentralGoogle Scholar
  402. Snyder PW, Kazacos EA, Scott-Moncrieff JC et al (1995) Pathologic features of naturally occurring juvenile polyarteritis in beagle dogs. Vet Pathol 32:337–345PubMedCrossRefPubMedCentralGoogle Scholar
  403. Sokolowski JH, Zimbelman RG (1973) Canine reproduction: effects of a single injection of medroxyprogesterone acetate on the reproductive organs of the bitch. Am J Vet Res 34:1493–1499PubMedPubMedCentralGoogle Scholar
  404. Sorenmo KU, Rasotto R, Zappulli V, Goldschmidt MH (2010) Development, anatomy, histology, lymphatic drainage, clinical features, and cell differentiation markers of canine mammary neoplasms. Vet Pathol 48:85–97PubMedCrossRefPubMedCentralGoogle Scholar
  405. Sourla A, Martel C, Labrie C, Labrie F (1998a) Almost exclusive androgenic action of dehydroepiandrosterone in the rat mammary gland. Endocrinology 139:753–764PubMedCrossRefPubMedCentralGoogle Scholar
  406. Sourla A, Flamand M, Bélanger A, Labrie F (1998b) Effect of dehydroepiandrosterone on vaginal and uterine histomorphology in the rat. J Steroid Biochem Mol Biol 66:137–149PubMedCrossRefPubMedCentralGoogle Scholar
  407. Steiner RA, Bremner WJ (1981) Endocrine correlates of sexual development in the male monkey, Macaca fascicularis. Endocrinology 109:914–919PubMedCrossRefPubMedCentralGoogle Scholar
  408. Sternlicht MD (2006) The cues that regulate ductal branching morphogenesis. Breast Cancer Res 8:201–211PubMedCrossRefPubMedCentralGoogle Scholar
  409. Stouffer RL (2006) Structure, function, and regulation of the corpus luteum. In: Neill JD (ed) Knobil and Neill’s physiology of reproduction, 3rd edn. Elsevier, San Diego, pp 475–526CrossRefGoogle Scholar
  410. Strange R, Westerlind KC, Ziemiecki A, Andres AC (2007) Proliferation and apoptosis in mammary epithelium during the rat estrous cycle. Acta Physiol 190:137–149CrossRefGoogle Scholar
  411. Strickland JL, Wall JW (2003) Abnormal uterine bleeding in adolescents. Obstet Gynecol Clin North Am 30(2):321–335. Review. PubMed PMID: 12836723PubMedCrossRefPubMedCentralGoogle Scholar
  412. Suen A, Jefferson W, Wood CE, Padilla-Banks E, Bae-Jump VL, Williams CJ (2016) SIX1 oncoprotein as a biomarker in a model of hormonal carcinogenesis and in human endometrial cancer. Mol Cancer Res 14:849–858PubMedPubMedCentralCrossRefGoogle Scholar
  413. Taberner E, Navratil N, Jasmin B, Salerno M, Grambo B, Althouse GC (2016) Pubertal age based on testicular and epididymal histology in Göttingen minipigs. Theriogenology 86(9):2091–2095.  https://doi.org/10.1016/j.theriogenology.2015.07.030. Epub 2015 Jul 29. PubMed PMID: 27613251CrossRefPubMedPubMedCentralGoogle Scholar
  414. Takayama S, Akaike M, Kawashima K, Takahashi M, Kurokawa Y (1995) Studies on the optimal treatment period and parameters for detection of male fertility disorder in rats--introductory summary. J Toxicol Sci 20(3):173–182. PubMed PMID: 8667444PubMedCrossRefPubMedCentralGoogle Scholar
  415. Taketa Y, Inomata A, Hosokawa S et al (2011) Histopathological characteristics of luteal hypertrophy induced by ethylene glycol monomethyl ether with a comparison to normal luteal morphology in rats. Toxicol Pathol 39:372–380PubMedCrossRefPubMedCentralGoogle Scholar
  416. Tang FY, Bonfiglio TA, Tang LK (1984) Effect of estrogen and progesterone on the development of endometrial hyperplasia in the Fischer rat. Biol Reprod 31:399–413PubMedCrossRefPubMedCentralGoogle Scholar
  417. Tangbanluekal L, Robinette CL (1993) Prolactin mediates estradiol-induced inflammation in the lateral prostate of Wistar rats. Endocrinology 132:2407–2416PubMedCrossRefPubMedCentralGoogle Scholar
  418. Tani Y, Foster PM, Sills RC, Chan PC, Peddada SD, Nyska A (2005) Epididymal sperm granuloma induced by chronic administration of 2-methyoimidazole in B6C3F1 mice. Toxicol Pathol 33:313–319PubMedCrossRefPubMedCentralGoogle Scholar
  419. Tarara RP (2007) Review of mammary gland neoplasia in nonhuman primates. Breast Dis 28:23–27PubMedCrossRefPubMedCentralGoogle Scholar
  420. Thuilliez C, Tortereau A, Perron-Lepage MF, Howroyd P, Gauthier B (2014) Spontaneous testicular tubular hypoplasia/atrophy in the Göttingen minipig: a retrospective study. Toxicol Pathol 42(6):1024–1031.  https://doi.org/10.1177/0192623313512430. Epub 2013 Nov 28. PubMed PMID: 24292387CrossRefPubMedPubMedCentralGoogle Scholar
  421. Tibbetts TA, Mendoza-Meneses M, O’Malley BW, Conneely OM (1998) Mutual and intercompartmental regulation of estrogen receptor and progesterone receptor expression in the mouse uterus. Biol Reprod 59:1143–1152PubMedCrossRefPubMedCentralGoogle Scholar
  422. Topper YJ, Freeman CS (1980) Multiple hormone interactions in the developmental biology of the mammary gland. Physiol Rev 60:1049–1106PubMedCrossRefPubMedCentralGoogle Scholar
  423. Tortereau A, Howroyd P, Lorentsen H (2013) Onset of puberty and normal histological appearances of the reproductive organs in peripubertal female Göttingen minipigs. Toxicol Pathol 41(8):1116–1125.  https://doi.org/10.1177/0192623313482777. Epub 2013 May 7. PubMed PMID: 23651587CrossRefPubMedPubMedCentralGoogle Scholar
  424. Toyoda K, Shibutani M, Tamura T, Koujitani T, Uneyama C, Hirose M (2000) Repeated dose (28 days) oral toxicity study of flutamide in rats, based on the draft protocol for the “Enhanced OECD Test Guideline 407” for screening for endocrine-disrupting chemicals. Arch Toxicol 74:127–132PubMedCrossRefPubMedCentralGoogle Scholar
  425. Troiano L, Fustini MF, Lovato E et al (1994) Apoptosis and spermatogenesis: evidence from an in vivo model of testosterone withdrawal in the adult rat. Biochem Biophys Res Commun 202:1315–1321PubMedCrossRefPubMedCentralGoogle Scholar
  426. Tsubota K, Kushima K, Yamauchi K et al (2009) Collaborative work on evaluation of ovarian toxicity. 12. Effects of 2- or 4-week repeated dose studies and fertility study of indomethacin in female rats. J Toxicol Sci 34:SP129–SP136PubMedCrossRefPubMedCentralGoogle Scholar
  427. Tsujioka S, Ban Y, Wise LD et al (2009) Collaborative work on evaluation of ovarian toxicity. 3. Effects of 2- or 4- week repeated dose toxicity and fertility studies with tamoxifen in female rats. J Toxicol Sci 34:SP43–SP51PubMedCrossRefPubMedCentralGoogle Scholar
  428. Tucker DK, Macon MB, Strynar MJ, Dagnino S, Andersen E, Fenton SE (2015) The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure. Reprod Toxicol 54:26–36.  https://doi.org/10.1016/j.reprotox.2014.12.002CrossRefPubMedPubMedCentralGoogle Scholar
  429. Turner C, Gomez E (1934) The normal development of the mammary gland of the male and female albino mouse. Mo Agr Exp Stn Res Bull 182:3–20Google Scholar
  430. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (2015) Testicular toxicity: evaluation during drug development guidance for industry, draft guidance. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM455102.pdf. Accessed 25 Feb 2018
  431. Udagawa K, Ogawa T, Watanabe T, Tamura Y, Kita K, Kubota Y (2006) Testosterone administration promotes regeneration of chemically impaired spermatogenesis in rats. Int J Urol 13(8):1103–1108. PubMed PMID: 16903937PubMedCrossRefPubMedCentralGoogle Scholar
  432. Van Der Lee S, Boot LM (1955) Spontaneous pseudopregnancy in mice. Acta Physiol Pharmacol Neerl 4(3):442–444. PubMed PMID: 13301816Google Scholar
  433. van der Schoot P, Bakker GH, Klijn JGM (1987) Effects of the progesterone antagonist RU486 on ovarian activity in the rat. Endocrinology 121:1375–1382PubMedCrossRefPubMedCentralGoogle Scholar
  434. van Esch E, Cline JM, Buse E, Weinbauer GF (2008) The macaque endometrium, with special reference to the cynomolgus monkey (Macaca fascicularis). Toxicol Pathol 36:67S–100SCrossRefGoogle Scholar
  435. van Wagenen G, Simpson ME (1973) Postnatal development of the ovary in Homo sapiens and Macaca mulatta and induction of ovulation in the macaque. Yale University Press, New HavenGoogle Scholar
  436. van Zwieten MJ, HogenEsch H, Majka JA, Boorman GA (1994) Nonneoplastic and neoplastic lesions of the mammary gland. In: Mohr U, Dungworth DL, Capen CC (eds) Pathobiology of the aging rat, vol 2. ILSI Press, Washington, DC, pp 459–476Google Scholar
  437. Vermeirsch H, Van Den Broeck W, Simeons P (2002) Immunolocalization of sex steroid hormone receptors in canine vaginal and vulvar tissue and their relation to sex steroid hormone concentrations. Reprod Fertil Dev 14:251–258PubMedCrossRefPubMedCentralGoogle Scholar
  438. Vidal JD (2017) The impact of age on the female reproductive system. Toxicol Pathol 45(1):206–215.  https://doi.org/10.1177/0192623316673754. Epub 2016 Oct 17. Review. PubMed PMID: 27753638CrossRefPubMedPubMedCentralGoogle Scholar
  439. Vidal JD, Filgo AJ (2017) Evaluation of the estrous cycle, reproductive tract, and mammary gland in female mice. Curr Protoc Mouse Biol 7(4):306–325.  https://doi.org/10.1002/cpmo.35. PubMed PMID: 29261233CrossRefPubMedPubMedCentralGoogle Scholar
  440. Vidal JD, Whitney KM (2014) Morphologic manifestations of testicular and epididymal toxicity. Spermatogenesis 4(2):e979099.  https://doi.org/10.4161/21565562.2014.979099CrossRefPubMedPubMedCentralGoogle Scholar
  441. Vidal JD, Mirsky ML, Coleman K, Whitney KM, Creasy D (2013) Reproductive system and mammary gland. In: Sahota PS, Popp JA, Hardisty JF, Gopinath C (eds) Toxicologic pathology: nonclinical safety assessment. Taylor & Francis, Boca RatonGoogle Scholar
  442. vom Saal FS, Finch CE, Nelson JF (1994) Natural history and mechanisms of reproductive aging in humans, laboratory rodents, and other selected vertebrates. In: Knobil E, Neill JD (eds) The physiology of reproduction, 2nd edn. Raven Press, New York, pp 1213–1314Google Scholar
  443. Von Berky AG, Townsend WL (1993) The relationship between the prevalence of uterine lesions and the use of medroxyprogesterone acetate for canine population control. Aust Vet J 70:249–250CrossRefGoogle Scholar
  444. Walker ML, Gordon TP, Wilson ME (1983) Menstrual cycle characteristics of seasonally breeding rhesus monkeys. Biol Reprod 29(4):841–848. PubMed PMID: 6416317PubMedCrossRefPubMedCentralGoogle Scholar
  445. Walker RF, Schwartz LW, Manson JM (1988) Ovarian effects of an anti-inflammatory-immunomodulatory drug in the rat. Toxicol Appl Pharmacol 94:266–275PubMedCrossRefPubMedCentralGoogle Scholar
  446. Wang H, Eriksson H, Sahlin L (2000) Estrogen receptors alpha and beta in the female reproductive tract of the rat during the estrous cycle. Biol Reprod 63:1331–1340PubMedCrossRefPubMedCentralGoogle Scholar
  447. Wang XJ, Bartolucci-Page E, Fenton SE, You L (2006) Altered mammary gland development in male rats exposed to genistein and methoxychlor. Toxicol Sci 91:93–103PubMedCrossRefPubMedCentralGoogle Scholar
  448. Wassarman P, Chen J, Cohen N et al (1999) Structure and function of the mammalian egg zona pellucida. J Exp Zool 285:251–258PubMedCrossRefPubMedCentralGoogle Scholar
  449. Weinbauer GF, Niehoff M, Niehaus M, Srivastav S, Fuchs A, Van Esch E, Cline JM (2008) Physiology and endocrinology of the ovarian cycle in macaques. Toxicol Pathol 36:7S–23SPubMedPubMedCentralCrossRefGoogle Scholar
  450. Welsch CW, Nagasawa H, Meites J (1970) Increased incidence of spontaneous mammary tumors in female rats with induced hypothalamic lesions. Cancer Res 30:2310–2313PubMedPubMedCentralGoogle Scholar
  451. Wenzel JGW, Odend’hal S (1985) The mammalian rete ovarii: a literature review. Cornell Vet 75:411–425PubMedPubMedCentralGoogle Scholar
  452. Westwood FR (2008) The female rat reproductive cycle: a practical histological guide to staging. Toxicol Pathol 36:375–384PubMedCrossRefPubMedCentralGoogle Scholar
  453. Wetzel LT, Luempert LG 3rd, Breckenridge CB, Tisdel MO, Stevens JT, Thakur AK, Extrom PJ, Eldridge JC (1994) Chronic effects of atrazine on estrus and mammary tumor formation in female Sprague-Dawley and Fischer 344 rats. J Toxicol Environ Health 43(2):169–182. PubMed PMID: 7932847PubMedCrossRefPubMedCentralGoogle Scholar
  454. Whitney KM (2012) Testicular histopathology in juvenile rat toxicity studies. Syst Biol Reprod Med 58:51–56PubMedCrossRefPubMedCentralGoogle Scholar
  455. Wildt DE, Seager SWJ, Chakraborty PK (1981) Behavioral, ovarian and endocrine relationships in the pubertal bitch. J Anim Sci 53:182–191PubMedCrossRefPubMedCentralGoogle Scholar
  456. Wood CE (2008) Morphologic and immunohistochemical features of the cynomolgus macaque cervix. Toxicol Pathol 36:119S–129SCrossRefGoogle Scholar
  457. Wood CE, Usborne AL, Starost MF et al (2006) Hyperplastic and neoplastic lesions of the mammary gland in macaques. Vet Pathol 43:471–483PubMedCrossRefPubMedCentralGoogle Scholar
  458. Wood CE, Hester JM, Cline JM (2007) Mammary gland development in early pubertal female macaques. Toxicol Pathol 35:793–803CrossRefGoogle Scholar
  459. Wood CE, Hester JM, Appt SE, Geisinger KR, Cline JM (2008) Estrogen effects on epithelial proliferation and benign proliferative lesions in the postmenopausal primate mammary gland. Lab Investig 88:938–948PubMedCrossRefPubMedCentralGoogle Scholar
  460. Wood CE, Kaplan JR, Fontenot MB, Williams JK, Cline JM (2010) Endometrial profile of tamoxifen and low-dose estradiol combination therapy. Clin Cancer Res 16:946–956PubMedPubMedCentralCrossRefGoogle Scholar
  461. Wood CE, Stavisky RC, Nowak J, Kaplan JR (2012) Stimulatory adrenocortical effects of a selective estrogen receptor modulator in ovariectomized female macaques. Toxicol Pathol 40:55–61PubMedCrossRefPubMedCentralGoogle Scholar
  462. Wood CE, Branstetter D, Jacob AP, Cline JM, Register TC, Rohrbach K, Huang LY, Borgerink H, Dougall WC (2013) Progestin effects on cell proliferation pathways in the postmenopausal mammary gland. Breast Cancer Res 15(4):R62PubMedPubMedCentralCrossRefGoogle Scholar
  463. Wordinger RJ, Morrill A (1985) Histology of the adult mouse oviduct and endometrium following a single prenatal exposure to diethylstilbestrol. Virchows Arch B Cell Pathol Incl Mol Pathol 50:71–79PubMedCrossRefPubMedCentralGoogle Scholar
  464. Wuttke W, Meites J (1971) Luteolytic role of prolactin during the estrous cycle of the rat. Proc Soc Exp Biol Med 137:988–991PubMedCrossRefPubMedCentralGoogle Scholar
  465. Yaghmaei P, Parivar K, Jalalvand F (2009) Effect of imatinib on the oogenesis and pituitary -ovary hormonal axis in female Wistar rat. Int J Fertil Steril 3:11–16Google Scholar
  466. Yamasaki K, Sawaki M, Noda S, Imatanaka N, Takatsuki M (2002) Subacute oral toxicity study of ethynylestradiol and bisphenol A, based on the draft protocol for the “Enhanced OECD Test Guideline no. 407”. Arch Toxicol 76:65–74PubMedCrossRefPubMedCentralGoogle Scholar
  467. Yeh S, Hu YC, Wang PH et al (2003) Abnormal mammary gland development and growth retardation in female mice and MCF7 breast cancer cells lacking androgen receptor. J Exp Med 198:1899–1908PubMedPubMedCentralCrossRefGoogle Scholar
  468. Yeh J, Kim BS, Liang YJ, Peresie J (2009) Gonadotropin stimulation as a challenge to calibrate cisplatin induced ovarian damage in the female rat. Reprod Toxicol 28:556–562PubMedCrossRefPubMedCentralGoogle Scholar
  469. Young JM, McNeilly AS (2010) Theca: the forgotten cell of the ovarian follicle. Reproduction 140:489–504PubMedCrossRefPubMedCentralGoogle Scholar
  470. Yuan YD, Carlson RG (1985) Structure, cyclic change, and function vagina and vulva, rat. In: Jones TC, Mohr U, Hunt RD (eds) Genital system. Springer-Verlag, Berlin, pp 161–168Google Scholar
  471. Yuan YD, Foley GL (2002) Female reproductive system. In: Haschek WM, Rousseaux CG, Wallig MA (eds) Handbook of toxicologic pathology, vol 2, 2nd edn. Academic Press, San Diego, pp 847–894CrossRefGoogle Scholar
  472. Zondervan KT, Weeks DE, Colman R, Cardon LR, Hadfield R, Schleffler J, Trainor AG, Coe CL, Kemnitz JW, Kennedy SH (2004) Familial aggregation of endometriosis in a large pedigree of rhesus macaques. Hum Reprod 19:448–455PubMedCrossRefPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Charles River Laboratories, Inc.MattawanUSA

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