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The roles and mechanisms of Leydig cells and myoid cells in regulating spermatogenesis

  • Rui Zhou
  • Jingrouzi Wu
  • Bang Liu
  • Yiqun Jiang
  • Wei Chen
  • Jian Li
  • Quanyuan He
  • Zuping HeEmail author
Review
  • 125 Downloads

Abstract

Spermatogenesis is fundamental to the establishment and maintenance of male reproduction, whereas its abnormality results in male infertility. Somatic cells, including Leydig cells, myoid cells, and Sertoli cells, constitute the microenvironment or the niche of testis, which is essential for regulating normal spermatogenesis. Leydig cells are an important component of the testicular stroma, while peritubular myoid cells are one of the major cell types of seminiferous tubules. Here we addressed the roles and mechanisms of Leydig cells and myoid cells in the regulation of spermatogenesis. Specifically, we summarized the biological features of Leydig cells and peritubular myoid cells, and we introduced the process of testosterone production and its major regulation. We also discussed other hormones, cytokines, growth factors, transcription factors and receptors associated with Leydig cells and myoid cells in mediating spermatogenesis. Furthermore, we highlighted the issues that are worthy of further studies in the regulation of spermatogenesis by Leydig cells and peritubular myoid cells. This review would provide novel insights into molecular mechanisms of the somatic cells in controlling spermatogenesis, and it could offer new targets for developing therapeutic approaches of male infertility.

Keywords

Leydig cells Myoid cells Spermatogenesis Hormones Cytokines Growth factors Transcription factors Receptors 

Notes

Acknowledgements

This work was supported by Grants from National Nature Science Foundation of China (General Programme, 31671550, 31872845, Key Programme, 31230048), Chinese Ministry of Science and Technology (2016YFC1000606), High Level Talent Gathering Project in Hunan Province (2018RS3066), The Open Fund of the NHC Key Laboratory of Male Reproduction and Genetics (KF201802), and Shanghai Hospital Development Center (SHDC12015122).

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.

References

  1. 1.
    Schulz RW et al (2010) Spermatogenesis in fish. Gen Comp Endocrinol 165:390–411CrossRefPubMedGoogle Scholar
  2. 2.
    Hai Y et al (2014) The roles and regulation of Sertoli cells in fate determinations of spermatogonial stem cells and spermatogenesis. Semin Cell Dev Biol 29:66–75CrossRefPubMedGoogle Scholar
  3. 3.
    Mendis-Handagama SM, Ariyaratne HB (2001) Differentiation of the adult Leydig cell population in the postnatal testis. Biol Reprod 65:660–671CrossRefPubMedGoogle Scholar
  4. 4.
    Shima Y et al (2013) Contribution of Leydig and Sertoli cells to testosterone production in mouse fetal testes. Mol Endocrinol 27:63–73CrossRefPubMedGoogle Scholar
  5. 5.
    De Gendt K et al (2004) A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc Natl Acad Sci USA 101:1327–1332CrossRefPubMedGoogle Scholar
  6. 6.
    Willems A et al (2015) Sertoli cell androgen receptor signalling in adulthood is essential for post-meiotic germ cell development. Mol Reprod Dev 82:626–627CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Welsh M, Saunders PTK, Atanassova N, Sharpe RM, Smith LB (2009) Androgen action via testicular peritubular myoid cells is essential for male fertility. FASEB J 23:4218–4230CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    O’Shaughnessy PJ, Verhoeven G, De Gendt K, Monteiro A, Abel MH (2010) Direct action through the Sertoli cells is essential for androgen stimulation of spermatogenesis. Endocrinology 151:2343–2348CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Haider SG (2004) Cell biology of Leydig cells in the testis. Int Rev Cytol 233:181–241CrossRefPubMedGoogle Scholar
  10. 10.
    Svechnikov K et al (2010) Origin, development and regulation of human Leydig cells. Hormone Res Paediatr 73:93–101CrossRefGoogle Scholar
  11. 11.
    Wang YQ, Chen SR, Liu YX (2018) Selective deletion of WLS in peritubular myoid cells does not affect spermatogenesis or fertility in mice. Mol Reprod Dev 85:559–561CrossRefPubMedGoogle Scholar
  12. 12.
    Richardson LL, Kleinman HK, Dym M (1995) Basement membrane gene expression by Sertoli and peritubular myoid cells in vitro in the rat. Biol Reprod 52:320–330CrossRefPubMedGoogle Scholar
  13. 13.
    Skinner MK, Tung PS, Fritz IB (1985) Cooperativity between Sertoli cells and testicular peritubular cells in the production and deposition of extracellular matrix components. J Cell Biol 100:1941–1947CrossRefPubMedGoogle Scholar
  14. 14.
    Mayerhofer A (2013) Human testicular peritubular cells: more than meets the eye. Reproduction 145:R107–R116CrossRefPubMedGoogle Scholar
  15. 15.
    Huleihel M, Lunenfeld E (2004) Regulation of spermatogenesis by paracrine/autocrine testicular factors. Asian J Androl 6:259–268PubMedGoogle Scholar
  16. 16.
    Bagatell CJ, Heiman JR, Rivier JE, Bremner WJ (1994) Effects of endogenous testosterone and estradiol on sexual behavior in normal young men. J Clin Endocrinol Metab 78:711–716PubMedGoogle Scholar
  17. 17.
    Antonio-Cabrera E, Paredes RG (2012) Effects of chronic estradiol or testosterone treatment upon sexual behavior in sexually sluggish male rats. Pharmacol Biochem Be 101:336–341CrossRefGoogle Scholar
  18. 18.
    Jarow JP, Zirkin BR (2005) The androgen microenvironment of the human testis and hormonal control of spermatogenesis. Ann N Y Acad Sci 1061:208–220CrossRefPubMedGoogle Scholar
  19. 19.
    Chang JA, Nguyen HT, Lue TF (2002) Surgical management: saphenous vein grafts. Int J Impot Res 14:375–378CrossRefPubMedGoogle Scholar
  20. 20.
    Collins LL, Chang C (2002) Androgens and the androgen receptor in male sex development and fertility. Springer US, New YorkCrossRefGoogle Scholar
  21. 21.
    Quigley CA (1998) The androgen receptor: physiology and pathophysiology. Springer, BerlinGoogle Scholar
  22. 22.
    Lin TH, Yeh S, Chang C (2011) Tissue-specific knockout of androgen receptor in mice. Methods Mol Biol 776:275–293CrossRefPubMedGoogle Scholar
  23. 23.
    Manna PR et al (2013) Mechanisms of action of hormone-sensitive lipase in mouse Leydig cells: its role in the regulation of the steroidogenic acute regulatory protein. J Biol Chem 288:8505–8518CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Zhong L, Sun J, Liu GH, Zhu YJ, Zhu J (2013) Research on the steroidogenesis of proliferated Leydig cells in vitro. J Artif Organs 16:229–233CrossRefPubMedGoogle Scholar
  25. 25.
    Abarikwu SO, Pant AB, Farombi EO (2013) Effects of quercetin on mRNA expression of steroidogenesis genes in primary cultures of Leydig cells treated with atrazine. Toxicol In Vitro 27:700–707CrossRefPubMedGoogle Scholar
  26. 26.
    Turner TT et al (1984) On the androgen microenvironment of maturing spermatozoa. Endocrinology 115:1925–1932CrossRefPubMedGoogle Scholar
  27. 27.
    Bartlett JM, 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 7:240–253CrossRefPubMedGoogle Scholar
  28. 28.
    O’Donnell L, McLachlan RI, Wreford NG, Robertson DM (1994) Testosterone promotes the conversion of round spermatids between stages VII and VIII of the rat spermatogenic cycle. Endocrinology 135:2608–2614CrossRefPubMedGoogle Scholar
  29. 29.
    O’Donnell L, McLachlan RI, Wreford NG, de Kretser DM, Robertson DM (1996) Testosterone withdrawal promotes stage-specific detachment of round spermatids from the rat seminiferous epithelium. Biol Reprod 55:895–901CrossRefPubMedGoogle Scholar
  30. 30.
    Haywood M et al (2003) Sertoli and germ cell development in hypogonadal (hpg) mice expressing transgenic follicle-stimulating hormone alone or in combination with testosterone. Endocrinology 144:509–517CrossRefPubMedGoogle Scholar
  31. 31.
    Stanton PG et al (2012) Proteomic changes in rat spermatogenesis in response to in vivo androgen manipulation; impact on meiotic cells. PLoS One 7:e41718CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Holdcraft RW, Braun RE (2004) Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids. Development 131:459–467CrossRefPubMedGoogle Scholar
  33. 33.
    O’Donnell L et al (2009) Transcriptional profiling of the hormone-responsive stages of spermatogenesis reveals cell-, stage-, and hormone-specific events. Endocrinology 150:5074–5084CrossRefPubMedGoogle Scholar
  34. 34.
    Pelletier RM (2011) The blood-testis barrier: the junctional permeability, the proteins and the lipids. Prog Histochem Cytochem 46:49–127CrossRefPubMedGoogle Scholar
  35. 35.
    Kopera IA, Bilinska B, Cheng CY, Mruk DD (2010) Sertoli-germ cell junctions in the testis: a review of recent data. Philos Trans R Soc Lond Ser B Biol Sci 365:1593–1605CrossRefGoogle Scholar
  36. 36.
    Chauvigne F et al (2012) Follicle-stimulating hormone and luteinizing hormone mediate the androgenic pathway in Leydig cells of an evolutionary advanced teleost. Biol Reprod 87:35CrossRefPubMedGoogle Scholar
  37. 37.
    Aghazadeh Y, Zirkin BR, Papadopoulos V (2015) Pharmacological regulation of the cholesterol transport machinery in steroidogenic cells of the testis. Vitam Horm 98:189–227CrossRefPubMedGoogle Scholar
  38. 38.
    Wang Y, Chen F, Ye L, Zirkin B, Chen H (2017) Steroidogenesis in Leydig cells: effects of aging and environmental factors. Reproduction 154:R111–R122CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Bourguiba S, Genissel C, Lambard S, Bouraima H, Carreau S (2003) Regulation of aromatase gene expression in Leydig cells and germ cells. J Steroid Biochem Mol Biol 86:335–343CrossRefPubMedGoogle Scholar
  40. 40.
    Cooke BA et al (1991) Release of arachidonic acid and the effects of corticosteroids on steroidogenesis in rat testis Leydig cells. J Steroid Biochem Mol Biol 40:465–471CrossRefPubMedGoogle Scholar
  41. 41.
    Duarte A et al (2007) An arachidonic acid generation/export system involved in the regulation of cholesterol transport in mitochondria of steroidogenic cells. FEBS Lett 581:4023–4028CrossRefPubMedGoogle Scholar
  42. 42.
    Hatano M et al (2016) SF-1 deficiency causes lipid accumulation in Leydig cells via suppression of STAR and CYP11A1. Endocrine 54:484–496CrossRefPubMedGoogle Scholar
  43. 43.
    Wajda A et al (2017) Cell and region specificity of aryl hydrocarbon receptor (AhR) system in the testis and the epididymis. Reprod Toxicol 69:286–296CrossRefPubMedGoogle Scholar
  44. 44.
    McCoard SA, Wise TH, Fahrenkrug SC, Ford JJ (2001) Temporal and spatial localization patterns of Gata4 during porcine gonadogenesis. Biol Reprod 65:366–374CrossRefPubMedGoogle Scholar
  45. 45.
    Schrade A et al (2015) GATA4 is a key regulator of steroidogenesis and glycolysis in mouse Leydig cells. Endocrinology 156:1860–1872CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Shimizu-Albergine M et al (2016) SCAP/SREBP pathway is required for the full steroidogenic response to cyclic AMP. Proc Natl Acad Sci USA 113:E5685–E5693CrossRefPubMedGoogle Scholar
  47. 47.
    Takemori H et al (2007) Dephosphorylation of TORC initiates expression of the StAR gene. Mol Cell Endocrinol 265–266:196–204CrossRefPubMedGoogle Scholar
  48. 48.
    Chen H et al (2015) Knockout of the transcription factor Nrf2: effects on testosterone production by aging mouse Leydig cells. Mol Cell Endocrinol 409:113–120CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Di-Luoffo M, Daems C, Bergeron F, Tremblay JJ (2015) Novel targets for the transcription factors MEF2 in MA-10 Leydig cells. Biol Reprod 93:9CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Morgan JA et al (2012) Deregulated hepatic metabolism exacerbates impaired testosterone production in Mrp4-deficient mice. J Biol Chem 287:14456–14466CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Gazouli M et al (2002) Effect of peroxisome proliferators on Leydig cell peripheral-type benzodiazepine receptor gene expression, hormone-stimulated cholesterol transport, and steroidogenesis: role of the peroxisome proliferator-activator receptor alpha. Endocrinology 143:2571–2583CrossRefPubMedGoogle Scholar
  52. 52.
    Maira M, Martens C, Batsche E, Gauthier Y, Drouin J (2003) Dimer-specific potentiation of NGFI-B (Nur77) transcriptional activity by the protein kinase A pathway and AF-1-dependent coactivator recruitment. Mol Cell Biol 23:763–776CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Carreau S, Wolczynski S, Galeraud-Denis I (2010) Aromatase, oestrogens and human male reproduction. Philos Trans R Soc Lond Ser B Biol Sci 365:1571–1579CrossRefGoogle Scholar
  54. 54.
    Pak TR, Lynch GR, Tsai PS (2002) Estrogen accelerates gonadal recrudescence in photo-regressed male siberian hamsters. Endocrinology 143:4131–4134CrossRefPubMedGoogle Scholar
  55. 55.
    Schon J, Blottner S (2008) Estrogens are involved in seasonal regulation of spermatogenesis and sperm maturation in roe deer (Capreolus capreolus). Gen Comp Endocrinol 159:257–263CrossRefPubMedGoogle Scholar
  56. 56.
    Robertson KM, O’Donnell L, Simpson ER, Jones ME (2002) The phenotype of the aromatase knockout mouse reveals dietary phytoestrogens impact significantly on testis function. Endocrinology 143:2913–2921CrossRefPubMedGoogle Scholar
  57. 57.
    Rochira V et al (2005) Estrogens in males: what have we learned in the last 10 years? Asian J Androl 7:3–20CrossRefPubMedGoogle Scholar
  58. 58.
    Robertson KM et al (1999) Impairment of spermatogenesis in mice lacking a functional aromatase (cyp 19) gene. Proc Natl Acad Sci USA 96:7986–7991CrossRefPubMedGoogle Scholar
  59. 59.
    Robertson KM, Simpson ER, Lacham-Kaplan O, Jones ME (2001) Characterization of the fertility of male aromatase knockout mice. J Androl 22:825–830PubMedGoogle Scholar
  60. 60.
    Cho HW et al (2003) The antiestrogen ICI 182,780 induces early effects on the adult male mouse reproductive tract and long-term decreased fertility without testicular atrophy. Reprod Biol Endocrinol 1:57CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Oliveira CA, Carnes K, Franca LR, Hess RA (2001) Infertility and testicular atrophy in the antiestrogen-treated adult male rat. Biol Reprod 65:913–920CrossRefPubMedGoogle Scholar
  62. 62.
    Eddy EM et al (1996) Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility. Endocrinology 137:4796–4805CrossRefPubMedGoogle Scholar
  63. 63.
    Assinder S, Davis R, Fenwick M, Glover A (2007) Adult-only exposure of male rats to a diet of high phytoestrogen content increases apoptosis of meiotic and post-meiotic germ cells. Reproduction 133:11–19CrossRefPubMedGoogle Scholar
  64. 64.
    Watson ED, Nikolakopoulos E, Gilbert C, Goode J (1999) Oxytocin in the semen and gonads of the stallion. Theriogenology 51:855–865CrossRefPubMedGoogle Scholar
  65. 65.
    Assinder SJ, Carey M, Parkinson T, Nicholson HD (2000) Oxytocin and vasopressin expression in the ovine testis and epididymis: changes with the onset of spermatogenesis. Biol Reprod 63:448–456CrossRefPubMedGoogle Scholar
  66. 66.
    Frayne J, Nicholson HD (1995) Effect of oxytocin on testosterone production by isolated rat Leydig cells is mediated via a specific oxytocin receptor. Biol Reprod 52:1268–1273CrossRefPubMedGoogle Scholar
  67. 67.
    Thackare H, Nicholson HD, Whittington K (2006) Oxytocin—its role in male reproduction and new potential therapeutic uses. Hum Reprod Update 12:437–448CrossRefPubMedGoogle Scholar
  68. 68.
    Assinder SJ, Rezvani A, Nicholson HD (2002) Oxytocin promotes spermiation and sperm transfer in the mouse. Int J Androl 25:19–27CrossRefPubMedGoogle Scholar
  69. 69.
    Bay K et al (2005) Insulin-like factor 3 serum levels in 135 normal men and 85 men with testicular disorders: relationship to the luteinizing hormone-testosterone axis. J Clin Endocrinol Metab 90:3410–3418CrossRefPubMedGoogle Scholar
  70. 70.
    Kawamura K et al (2004) Paracrine regulation of mammalian oocyte maturation and male germ cell survival. Proc Natl Acad Sci USA 101:7323–7328CrossRefPubMedGoogle Scholar
  71. 71.
    Amory JK et al (2007) Elevated end-of-treatment serum INSL3 is associated with failure to completely suppress spermatogenesis in men receiving male hormonal contraception. J Androl 28:548–554CrossRefPubMedGoogle Scholar
  72. 72.
    Bardin CW et al (1984) Identification and possible function of pro-opiomelanocortin-derived peptides in the testis. Ann N Y Acad Sci 438:346–364CrossRefPubMedGoogle Scholar
  73. 73.
    Weil S, Degen AA, Friedlander M, Rosenstrauch A (1999) Low fertility in aging roosters is related to a high plasma concentration of insulin and low testicular contents of ACTH and lactate. Gen Comp Endocrinol 115:110–115CrossRefPubMedGoogle Scholar
  74. 74.
    Segarra AC, Luine VN, Strand FL (1991) Sexual behavior of male rats is differentially affected by timing of perinatal ACTH administration. Physiol Behav 50:689–697CrossRefPubMedGoogle Scholar
  75. 75.
    Nagata S et al (1998) Testicular inhibin in the stallion: cellular source and seasonal changes in its secretion. Biol Reprod 59:62–68CrossRefPubMedGoogle Scholar
  76. 76.
    Grieco V et al (2011) Inhibin-alpha immunohistochemical expression in mature and immature canine Sertoli and Leydig cells. Reprod Domest Anim 46:920–923CrossRefPubMedGoogle Scholar
  77. 77.
    Li Q et al (2016) Immunolocalization of inhibin/activin subunits and steroidogenic enzymes in the testes of an adult african elephant (Loxodonta africana). J Zoo Wildl Med 47:419–422CrossRefPubMedGoogle Scholar
  78. 78.
    Chaichanathong S et al (2018) Immunohistochemical localization of inhibin/activin subunits in adult Asian elephant (Elephas maximus) testes. J Vet Med Sci 80:549–552CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    van Dissel-Emiliani FM, Grootenhuis AJ, de Jong FH, de Rooij DG (1989) Inhibin reduces spermatogonial numbers in testes of adult mice and Chinese hamsters. Endocrinology 125:1899–1903PubMedGoogle Scholar
  80. 80.
    Kumanov P, Nandipati K, Tomova A, Agarwal A (2006) Inhibin B is a better marker of spermatogenesis than other hormones in the evaluation of male factor infertility. Fertil Steril 86:332–338CrossRefPubMedGoogle Scholar
  81. 81.
    Hedger MP, Winnall WR (2012) Regulation of activin and inhibin in the adult testis and the evidence for functional roles in spermatogenesis and immunoregulation. Mol Cell Endocrinol 359:30–42CrossRefPubMedGoogle Scholar
  82. 82.
    Hakovirta H, Kaipia A, Soder O, Parvinen M (1993) Effects of activin-A, inhibin-A, and transforming growth factor-beta 1 on stage-specific deoxyribonucleic acid synthesis during rat seminiferous epithelial cycle. Endocrinology 133:1664–1668CrossRefPubMedGoogle Scholar
  83. 83.
    Wang Y, Bilandzic M, Ooi GT, Findlay JK, Stenvers KL (2016) Endogenous inhibins regulate steroidogenesis in mouse TM3 Leydig cells by altering SMAD2 signalling. Mol Cell Endocrinol 436:68–77CrossRefPubMedGoogle Scholar
  84. 84.
    Yoon MJ, Berger T, Roser JF (2011) Localization of insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-IR) in equine testes. Reprod Domest Anim 46:221–228CrossRefPubMedGoogle Scholar
  85. 85.
    Yuan C, Chen K, Zhu Y, Yuan Y, Li M (2018) Medaka igf1 identifies somatic cells and meiotic germ cells of both sexes. Gene 642:423–429CrossRefPubMedGoogle Scholar
  86. 86.
    Muller L, Kowalewski MP, Reichler IM, Kollar E, Balogh O (2017) Different expression of leptin and IGF1 in the adult and prepubertal testis in dogs. Reprod Domest Anim 52(Suppl 2):187–192CrossRefPubMedGoogle Scholar
  87. 87.
    Zhang YQ et al (2004) Stage-specific localization of transforming growth factor beta1 and beta3 and their receptors during spermatogenesis in men. Asian J Androl 6:105–109PubMedGoogle Scholar
  88. 88.
    Abu Elheija M et al (2011) Distinct expression of interleukin-1alpha, interleukin-1beta, and interleukin-1 receptor antagonist in testicular tissues and cells from human biopsies with normal and abnormal histology. J Interf Cytokine Res 31:401–408CrossRefGoogle Scholar
  89. 89.
    Abu Elhija M, Lunenfeld E, Eldar-Geva T, Huleihel M (2008) Over-expression of IL-18, ICE and IL-18 R in testicular tissue from sexually immature as compared to mature mice. Eur Cytokine Netw 19:15–24PubMedGoogle Scholar
  90. 90.
    Frayne J, Nicholson HD (1998) Localization of oxytocin receptors in the human and macaque monkey male reproductive tracts: evidence for a physiological role of oxytocin in the male. Mol Hum Reprod 4:527–532CrossRefPubMedGoogle Scholar
  91. 91.
    O’Hara L, Smith LB (2015) Androgen receptor roles in spermatogenesis and infertility. Best Pract Res Clin Endocrinol Metab 29:595–605CrossRefPubMedGoogle Scholar
  92. 92.
    Han Y, Feng HL, Sandlow JI, Haines CJ (2009) Comparing expression of progesterone and estrogen receptors in testicular tissue from men with obstructive and nonobstructive azoospermia. J Androl 30:127–133CrossRefPubMedGoogle Scholar
  93. 93.
    Ivell R, Hartung S, Anand-Ivell R (2005) Insulin-like factor 3: where are we now? Ann N Y Acad Sci 1041:486–496CrossRefPubMedGoogle Scholar
  94. 94.
    Shiraishi K, Matsuyama H (2017) Gonadotoropin actions on spermatogenesis and hormonal therapies for spermatogenic disorders [Review]. Endocr J 64:123–131CrossRefPubMedGoogle Scholar
  95. 95.
    Herrera-Luna CV, Scarlet D, Walter I, Aurich C (2016) Effect of stallion age on the expression of LH and FSH receptors and aromatase P450 in equine male reproductive tissues. Reprod Fertil Dev 28:2016–2026CrossRefPubMedGoogle Scholar
  96. 96.
    Huhtaniemi I (2015) A short evolutionary history of FSH-stimulated spermatogenesis. Hormones 14:468–478PubMedGoogle Scholar
  97. 97.
    Curley M et al (2018) Leukemia inhibitory factor-receptor is dispensable for prenatal testis development but is required in Sertoli cells for normal spermatogenesis in mice. Sci Rep 8:11532CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    De SK et al (1993) Expression of tumor necrosis factor-alpha in mouse spermatogenic cells. Endocrinology 133:389–396CrossRefPubMedGoogle Scholar
  99. 99.
    Muller L, Kowalewski MP, Reichler IM, Kollar E, Balogh O (2017) Different expression of leptin and IGF1 in the adult and prepubertal testis in dogs. Reprod Domest Anim 52:187–192CrossRefPubMedGoogle Scholar
  100. 100.
    Olaso R, Pairault C, Habert R (1998) Expression of type I and II receptors for transforming growth factor beta in the adult rat testis. Histochem Cell Biol 110:613–618CrossRefPubMedGoogle Scholar
  101. 101.
    Caussanel V, Tabone E, Hendrick JC, Dacheux F, Benahmed M (1997) Cellular distribution of transforming growth factor betas 1, 2, and 3 and their types I and II receptors during postnatal development and spermatogenesis in the boar testis. Biol Reprod 56:357–367CrossRefPubMedGoogle Scholar
  102. 102.
    Chauvigne F, Parhi J, Olle J, Cerda J (2017) Dual estrogenic regulation of the nuclear progestin receptor and spermatogonial renewal during gilthead seabream (Sparus aurata) spermatogenesis. Comp Biochem Physiol Part A Mol Integr Physiol 206:36–46CrossRefGoogle Scholar
  103. 103.
    Braun BC, Okuyama MW, Muller K, Dehnhard M, Jewgenow K (2018) Steroidogenic enzymes, their products and sex steroid receptors during testis development and spermatogenesis in the domestic cat (Felis catus). J Steroid Biochem Mol Biol 178:135–149CrossRefPubMedGoogle Scholar
  104. 104.
    Manova K, Nocka K, Besmer P, Bachvarova RF (1990) Gonadal expression of c-kit encoded at the W locus of the mouse. Development 110:1057–1069PubMedGoogle Scholar
  105. 105.
    Rothschild G et al (2003) A role for kit receptor signaling in Leydig cell steroidogenesis. Biol Reprod 69:925–932CrossRefPubMedGoogle Scholar
  106. 106.
    Buehr M, McLaren A, Bartley A, Darling S (1993) Proliferation and migration of primordial germ cells in We/We mouse embryos. Dev Dyn 198:182–189CrossRefPubMedGoogle Scholar
  107. 107.
    Besmer P et al (1993) The kit-ligand (steel factor) and its receptor c-kit/W: pleiotropic roles in gametogenesis and melanogenesis. Development (Suppl):125–137Google Scholar
  108. 108.
    Huang EJ et al (1993) The murine steel panda mutation affects kit ligand expression and growth of early ovarian follicles. Dev Biol 157:100–109CrossRefPubMedGoogle Scholar
  109. 109.
    Oh YS, Seo JT, Ahn HS, Gye MC (2016) Expression of cubilin in mouse testes and Leydig cells. Andrologia 48:325–332CrossRefPubMedGoogle Scholar
  110. 110.
    Potter SJ, DeFalco T (2017) Role of the testis interstitial compartment in spermatogonial stem cell function. Reproduction 153:R151–R162CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Quigley CA et al (1995) Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev 16:271–321PubMedGoogle Scholar
  112. 112.
    Tan KA et al (2005) The role of androgens in Sertoli cell proliferation and functional maturation: studies in mice with total or Sertoli cell-selective ablation of the androgen receptor. Endocrinology 146:2674–2683CrossRefPubMedGoogle Scholar
  113. 113.
    Russell L, Bartke A, Goh J (1989) Postnatal development of the Sertoli cell barrier, tubular lumen, and cytoskeleton of Sertoli and myoid cells in the rat, and their relationship to tubular fluid secretion and flow. Am J Anat 184:179–189CrossRefPubMedGoogle Scholar
  114. 114.
    Denolet E et al (2006) The effect of a Sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice. Mol Endocrinol 20:321–334CrossRefPubMedGoogle Scholar
  115. 115.
    Baker PJ et al (2003) Failure of normal Leydig cell development in follicle-stimulating hormone (FSH) receptor-deficient mice, but not FSHbeta-deficient mice: role for constitutive FSH receptor activity. Endocrinology 144:138–145CrossRefPubMedGoogle Scholar
  116. 116.
    Welsh M et al (2012) Androgen receptor signalling in peritubular myoid cells is essential for normal differentiation and function of adult Leydig cells. Int J Androl 35:25–40CrossRefPubMedGoogle Scholar
  117. 117.
    Skinner MK, McLachlan RI, Bremner WJ (1989) Stimulation of Sertoli cell inhibin secretion by the testicular paracrine factor PModS. Mol Cell Endocrinol 66:239–249CrossRefPubMedGoogle Scholar
  118. 118.
    Verhoeven G et al (1992) The role of cell-cell interactions in androgen action. J Steroid Biochem Mol Biol 41:487–494CrossRefPubMedGoogle Scholar
  119. 119.
    Whaley PD, Chaudhary J, Cupp A, Skinner MK (1995) Role of specific response elements of the c-fos promoter and involvement of intermediate transcription factor(s) in the induction of Sertoli cell differentiation (transferrin promoter activation) by the testicular paracrine factor PModS. Endocrinology 136:3046–3053CrossRefPubMedGoogle Scholar
  120. 120.
    Wang YQ, Batool A, Chen SR, Liu YX (2018) GATA4 is a negative regulator of contractility in testicular peritubular myoid cells. ReproductionGoogle Scholar
  121. 121.
    Penny GM et al (2017) Probing GATA factor function in mouse Leydig cells via testicular injection of adenoviral vectors. Reproduction 156:343–351Google Scholar
  122. 122.
    Piquet-Pellorce C, Dorval-Coiffec I, Pham MD, Jegou B (2000) Leukemia inhibitory factor expression and regulation within the testis. Endocrinology 141:1136–1141CrossRefPubMedGoogle Scholar
  123. 123.
    Maekawa M, Kamimura K, Nagano T (1996) Peritubular myoid cells in the testis: their structure and function. Arch Histol Cytol 59:1–13CrossRefPubMedGoogle Scholar
  124. 124.
    Hoeben E (1997) Local control of Sertoli cell function: paracrine factors produced by peritubular myoid cells and cytokines. Coronet Books Incorporated, LondonGoogle Scholar
  125. 125.
    Chen LY, Willis WD, Eddy EM (2016) Targeting the Gdnf Gene in peritubular myoid cells disrupts undifferentiated spermatogonial cell development. Proc Natl Acad Sci USA 113:1829–1834CrossRefPubMedGoogle Scholar
  126. 126.
    Chen LY, Brown PR, Willis WB, Eddy EM (2014) Peritubular myoid cells participate in male mouse spermatogonial stem cell maintenance. Endocrinology 155:4964–4974CrossRefPubMedPubMedCentralGoogle Scholar
  127. 127.
    Oatley JM, Oatley MJ, Avarbock MR, Tobias JW, Brinster RL (2009) Colony stimulating factor 1 is an extrinsic stimulator of mouse spermatogonial stem cell self-renewal. Development 136:1191–1199CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    Ryan GR et al (2001) Rescue of the colony-stimulating factor 1 (CSF-1)-nullizygous mouse (Csf1(op)/Csf1(op)) phenotype with a CSF-1 transgene and identification of sites of local CSF-1 synthesis. Blood 98:74–84CrossRefPubMedGoogle Scholar
  129. 129.
    Yeh S et al (2002) Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues. Proc Natl Acad Sci USA 99:13498–13503CrossRefPubMedGoogle Scholar
  130. 130.
    Karpova T et al (2015) Steroidogenic factor 1 differentially regulates fetal and adult leydig cell development in male mice. Biol Reprod 93:83CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Bender AT, Beavo JA (2006) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 58:488–520CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Rui Zhou
    • 1
  • Jingrouzi Wu
    • 1
  • Bang Liu
    • 1
  • Yiqun Jiang
    • 1
  • Wei Chen
    • 1
  • Jian Li
    • 1
  • Quanyuan He
    • 1
  • Zuping He
    • 1
    Email author
  1. 1.Hunan Normal University School of MedicineChangshaChina

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