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Classification and Causes of Undescended Testes in Humans

  • John M. Hutson
  • Jørgen M. Thorup
  • Spencer W. Beasley
Chapter

Abstract

To understand the heterogeneous aetiology of cryptorchidism, a classification system is required. The classification is becoming clearer now that undescended testes (UDT) may be separated into congenital and ‘acquired’ types, and the recognition that ‘retractile’ testes form a grey zone between normally descended testes and those that may be developing to ascending, acquired UDT. Congenital UDT can be classified into intraabdominal UDT, canalicular, superficial inguinal pouch and prescrotal variants, aside from the rare ectopic testes. Acquired, ascending testes present later in childhood rather than at birth, and are thought to be caused by failure of the spermatic cord to elongate normally postnatally, so that the testis remains close to the inguinal canal as the scrotum grows away from the groin.The incidence of UDT was thought to be increasing but recent studies suggest this was just related to the use of different definitions of UDT. The aetiology remains mostly unknown, but is thought to be multifactorial. Genetic screening so far implicates muscle development and connective tissue remodelling in the aetiology.

Keywords

Inguinal Canal Undescended Testis Testicular Descent Patent Processus Vaginalis Nonpalpable Testis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Kaplan GW. Nomenclature of cryptorchidism. Eur J Pediatr. 1993;152 Suppl 2:S17–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Virtanen HE, Cortes D, Rajpert-De Meyts E, et al. Development and descent of the testis in relation to cryptorchidism. Acta Paediatr. 2007;96(5):622–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Hutson JM, Beasley SW. Descent of the testis. London: Edward Arnold; 1992. p. 1–87.Google Scholar
  4. 4.
    Wyllie GG. The diagnosis of undescended testes. Med J Aust. 1978;1(12):639–41.PubMedGoogle Scholar
  5. 5.
    Moul JW, Belman AB. A review of surgical treatment of undescended testes with emphasis on anatomical position. J Urol. 1988;140(1):125–8.PubMedGoogle Scholar
  6. 6.
    Cendron M, Huff DS, Keating MA, et al. Anatomical, morphological and volumetric analysis: a review of 759 cases of testicular maldescent. J Urol. 1993;149(3):570–3.PubMedGoogle Scholar
  7. 7.
    Cortes D, Thorup J, Frisch M, et al. Examination for intratubular germ cell neoplasia at operation for undescended testis in boys. J Urol. 1994;151(3):722–5.PubMedGoogle Scholar
  8. 8.
    Thorup J, Cortes D. Surgical treatment and follow up on undescended testis. Pediatr Endocrinol Rev. 2009;7(1):38–43.PubMedGoogle Scholar
  9. 9.
    Taran I, Elder JS. Results of orchiopexy for the undescended testis. World J Urol. 2006;24(3):231–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Baker LA, Docimo SG, Surer I, et al. A multi-institutional analysis of laparoscopic orchidopexy. BJU Int. 2001;87(6):484–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Hay SA, Soliman HA, Abdel Rahman AH, et al. Laparoscopic classification and treatment of the impalpable testis. Pediatr Surg Int. 1999;15(8):570–2.PubMedCrossRefGoogle Scholar
  12. 12.
    Samadi AA, Palmer LS, Franco I. Laparoscopic orchiopexy: report of 203 cases with review of diagnosis, operative technique, and lessons learned. J Endourol. 2003;17(6):365–8.PubMedCrossRefGoogle Scholar
  13. 13.
    El Gohary MA. Non-descent of the testis: an overlooked laparoscopic finding. J Pediatr Urol. 2008;4(5):364–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Chang B, Palmer LS, Franco I. Laparoscopic orchidopexy: a review of a large clinical series. BJU Int. 2001;87(6):490–3.PubMedCrossRefGoogle Scholar
  15. 15.
    Cortes D, Thorup JM, Lenz K, Beck BL, Nielson OH. Laparoscopy in 100 consecutive patients with 128 impalpable testes. Br J Urol. 1995;75:281–7.Google Scholar
  16. 16.
    Fowler R, Stephens FD. The role of testicular vascular anatomy in the salvage of high undescended testes. Aust N Z J Surg. 1959;29:92–106.PubMedCrossRefGoogle Scholar
  17. 17.
    Koff SA, Sethi PS. Treatment of high undescended testes by low spermatic vessel ligation: an alternative to the Fowler-Stephens technique. J Urol. 1996;156(2 Pt 2):799–803; discussion 803.PubMedGoogle Scholar
  18. 18.
    Ellis R, Lahiri R, Mahomed A. Mapping testicular blood supply in gubernaculum-sparing second-stage Fowler-Stephens procedure. Surg Endosc. 2014;28(11):3158–61.PubMedCrossRefGoogle Scholar
  19. 19.
    Browne D. Diagnosis of undescended testicle. Br Med J. 1938;2(4046):168–71.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Kolon TF, Herndon CD, Baker LA, et al. Evaluation and treatment of cryptorchidism: AUA guideline. J Urol. 2014;192(2):337–45.PubMedCrossRefGoogle Scholar
  21. 21.
    Annandale Y. Case in which a testicle congenitally displaced into the perineum was successfully transferred to the scrotom. Br Med J. 1879;1:7–8.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Thevasthasan CG. Transverse ectopia of the testis. Aust N Z J Surg. 1967;37:93–102.CrossRefGoogle Scholar
  23. 23.
    Beasley SW, Auldist AW. Crossed testicular ectopia in association with double incomplete testicular descent. Aust N Z J Surg. 1985;55(3):301–3.PubMedCrossRefGoogle Scholar
  24. 24.
    Hammoudi S. Transverse testicular ectopia. J Pediatr Surg. 1989;24(2):223–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Kimura T. Transverse ectopia of the testis with masculine uterus. Ann Surg. 1981;68:420–5.CrossRefGoogle Scholar
  26. 26.
    Hughes DT, Croitoru DP. Case report: crossed testicular ectopia. J Pediatr Surg. 2007;42(9):1620–2.PubMedCrossRefGoogle Scholar
  27. 27.
    Avolio L, Belville C, Bragheri R. Persistent mullerian duct syndrome with crossed testicular ectopia. Urology. 2003;62(2):350.PubMedCrossRefGoogle Scholar
  28. 28.
    Berg AA. VIII. Transverse ectopy of the testis. Ann Surg. 1904;40(2):223–4.PubMedCentralPubMedGoogle Scholar
  29. 29.
    Josso N. Development and descent of the fetal testis. In: Bierich JL, Rager K, Ranke MB, editors. Maldescensus testis. Munich: Urban and Schwarzenberg; 1977. p. 3–11.Google Scholar
  30. 30.
    Morris Jr MW, Cauthen W, Bofill JA, et al. Retroperitoneal lymphatic malformation and transverse testicular ectopia: a unique clinical presentation. J Pediatr Surg. 2013;48(4):e17–20.PubMedCrossRefGoogle Scholar
  31. 31.
    Naji H, Peristeris A, Stenman J, et al. Transverse testicular ectopia: three additional cases and a review of the literature. Pediatr Surg Int. 2012;28(7):703–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Scorer CG, Farrington GG. Congenital deformities of the testis and epididymis. London: Butterworths; 1971.Google Scholar
  33. 33.
    Kollin C, Hesser U, Ritzen EM, et al. Testicular growth from birth to two years of age, and the effect of orchidopexy at age nine months: a randomized, controlled study. Acta Paediatr. 2006;95(3):318–24.PubMedCrossRefGoogle Scholar
  34. 34.
    Keizer-Schrama SM, Hazebroek FW. Transverse ectopia of the testis with masculine uterus. Ann Surg. 1981;68:420–5.Google Scholar
  35. 35.
    Thorup J, Cortes D, Nielsen OH. Clinical and histopathological evaluation of operated maldescended testes after LH-RH treatment. Eur J Pediatr. 1993;152 Suppl 2:S37.PubMedCrossRefGoogle Scholar
  36. 36.
    Puri P, Nixon HH. Bilateral retractile testes – subsequent effects on fertility. J Pediatr Surg. 1977;12(4):563–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Rasmussen TB, Ingerslev HJ, Hostrup H. Natural history of the maldescended testis. Horm Res. 1988;30(4–5):164–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Thorup J, Cortes D. The incidence of maldescended testes in Denmark. Pediatr Surg Int. 1990;5:2–5.CrossRefGoogle Scholar
  39. 39.
    La Scala GC, Ein SH. Retractile testes: an outcome analysis on 150 patients. J Pediatr Surg. 2004;39(7):1014–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Villumsen AL, Zachau-Christiansen B. Spontaneous alterations in position of the testes. Arch Dis Child. 1966;41(216):198–200.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Atwell JD. Ascent of the testis: fact or fiction. Br J Urol. 1985;57(4):474–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Rabinowitz R, Hulbert Jr WC. Late presentation of cryptorchidism: the etiology of testicular re-ascent. J Urol. 1997;157(5):1892–4.PubMedCrossRefGoogle Scholar
  43. 43.
    Barthold JS, Gonzalez R. The epidemiology of congenital cryptorchidism, testicular ascent and orchiopexy. J Urol. 2003;170(6 Pt 1):2396–401.PubMedCrossRefGoogle Scholar
  44. 44.
    Mayr J, Rune GM, Holas A, et al. Ascent of the testis in children. Eur J Pediatr. 1995;154(11):893–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Dahl HM, Nerhus TK, Haga OS, et al. Ascent of the testis. Tidsskr Nor Laegeforen. 1995;115:598–600.PubMedGoogle Scholar
  46. 46.
    John Radcliffe Hospital Study Group. Clinical diagnosis of cryptorchidism. Arch Dis Child. 1988;63:587–91.CrossRefGoogle Scholar
  47. 47.
    Fenton EJM, Woodward AA, Hudson IL, et al. The ascending testis. Pediatr Surg Int. 1990;5:6–9.CrossRefGoogle Scholar
  48. 48.
    Donaldson KM, Tong SY, Hutson JM. Prevalence of late orchidopexy is consistent with some undescended testes being acquired. Indian J Pediatr. 1996;63(6):725–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Scorer CG. The descent of the testis. Arch Dis Child. 1964;39:605–9.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Bishop PMF. Studies in clinical endocrinology v the management of the undescended testis. Guys Hosp Rep. 1945;94:12–74.Google Scholar
  51. 51.
    Thonneau PF, Gandia P, Mieusset R. Cryptorchidism: incidence, risk factors, and potential role of environment; an update. J Androl. 2003;24(2):155–62.PubMedCrossRefGoogle Scholar
  52. 52.
    Toppari J, Kaleva M, Virtanen HE. Trends in the incidence of cryptorchidism and hypospadias, and methodological limitations of registry-based data. Hum Reprod Update. 2001;7(3):282–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Cortes D. Cryptorchidism – aspects of pathogenesis, histology and treatment. Scand J Urol Nephrol Suppl. 1998;196:1–54.PubMedGoogle Scholar
  54. 54.
    Boisen KA, Kaleva M, Main KM. Differences in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet. 2004;363:1264–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Berkowitz GS, Lapinski RH, Dolgin SE, et al. Prevalence and natural history of cryptorchidism. Pediatrics. 1993;92(1):44–9.PubMedGoogle Scholar
  56. 56.
    Buemann B, Henriksen H, Villumsen AL, et al. Incidence of undescended testis in the newborn. Acta Chir Scand Suppl. 1961;283(Suppl):289–93.PubMedGoogle Scholar
  57. 57.
    Cortes D, Kjellberg EM, Breddam M, et al. The true incidence of cryptorchidism in Denmark. J Urol. 2008;179:314–8.PubMedCrossRefGoogle Scholar
  58. 58.
    Hirasing RA, Grimberg R, Hirasing HD. Incidence of undescended testes in young children. Ned Tijdschr Geneeskd. 1982;126(50):2294–6.PubMedGoogle Scholar
  59. 59.
    Thong MK, Lim CT, Fatimah H. Undescended testes: incidence in 1002 consecutive male infants and outcome at 1 year of age. Pediatr Surg Int. 1998;13:37–41.PubMedCrossRefGoogle Scholar
  60. 60.
    Ghirri P, Ciulli C, Vuerich M, et al. Incidence at birth and natural history of cryptorchidism: a study of 10,730 consecutive male infants. J Endocrinol Invest. 2002;25(8):709–15.PubMedCrossRefGoogle Scholar
  61. 61.
    Preiksa RT, Zilaitiene B, Matulevicius V, et al. Higher than expected prevalence of congenital cryptorchidism in Lithuania: a study of 1204 boys at birth and 1 year follow-up. Hum Reprod. 2005;20(7):1928–32.PubMedCrossRefGoogle Scholar
  62. 62.
    Wohlfahrt-Veje C, Boisen KA, Boas M, et al. Acquired cryptorchidism is frequent in infancy and childhood. Int J Androl. 2009;32(4):423–8.PubMedCrossRefGoogle Scholar
  63. 63.
    Agarwal PK, Diaz M, Elder JS. Retractile testis – is it really a normal variant? J Urol. 2006;175(4):1496–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Ward B, Hunter WM. The absent testicle, a report on a survey carried out among schoolboys in Nottingham. Br Med J. 1960;1(5179):1110–1.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Blom K. Undescended testis and time of spontaneous descent in 2516 schoolboys. Ugeskr Laeger. 1984;146(8):616–7.PubMedGoogle Scholar
  66. 66.
    Han SW, Lee T, Kim JH, et al. Pathological difference between retractile and cryptorchid testes. J Urol. 1999;162(3 Pt 1):878–80.PubMedCrossRefGoogle Scholar
  67. 67.
    Rusnack SL, Wu HY, Huff DS, et al. The ascending testis and the testis undescended since birth share the same histopathology. J Urol. 2002;168(6):2590–1.PubMedCrossRefGoogle Scholar
  68. 68.
    Hack WW, Meijer RW, Van Der Voort-Doedens LM, et al. Previous testicular position in boys referred for an undescended testis: further explanation of the late orchidopexy enigma? BJU Int. 2003;92(3):293–6.PubMedCrossRefGoogle Scholar
  69. 69.
    Hutson JM, Hasthorpe S. Abnormalities of testicular descent. Cell Tissue Res. 2005;322(1):155–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Thorup J, Cortes D, Petersen BL. The incidence of bilateral cryptorchidism is increased and the fertility potential is reduced in sons born to mothers who have smoked during pregnancy. J Urol. 2006;176(2):734–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Chilvers C, Pike MC, Forman D, et al. Apparent doubling of frequency of undescended testis in England and Wales in 1962–81. Lancet. 1984;2(8398):330–2.PubMedCrossRefGoogle Scholar
  72. 72.
    Campbell DM, Webb JA, Hargreave TB. Cryptorchidism in Scotland. Br Med J (Clin Res Ed). 1987;295(6608):1235–6.CrossRefGoogle Scholar
  73. 73.
    Tamhne RC, Jarvis SN, Waterston AJ. Auditing community screening for undescended testes. Arch Dis Child. 1990;65(8):888–90.PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Jones ME, Swerdlow AJ, Griffith M, et al. Prenatal risk factors for cryptorchidism: a record linkage study. Paediatr Perinat Epidemiol. 1998;12(4):383–96.PubMedCrossRefGoogle Scholar
  75. 75.
    Toledano MB, Hansell AL, Jarup L, et al. Temporal trends in orchidopexy, Great Britain, 1992–1998. Environ Health Perspect. 2003;111(1):129–32.PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Capello SA, Giorgi Jr LJ, Kogan BA. Orchiopexy practice patterns in New York State from 1984 to 2002. J Urol. 2006;176(3):1180–3.PubMedCrossRefGoogle Scholar
  77. 77.
    Bonney T, Southwell B, Donnath S, et al. Orchidopexy trends in the paediatric population of Victoria, 1999–2006. J Pediatr Surg. 2009;44(2):427–31.PubMedCrossRefGoogle Scholar
  78. 78.
    Lee PA, Coughlin MT. Fertility after bilateral cryptorchidism. Evaluation by paternity, hormone, and semen data. Horm Res. 2001;55(1):28–32.PubMedCrossRefGoogle Scholar
  79. 79.
    Coughlin MT, Bellinger MF, Lee PA. Age at unilateral orchiopexy: effect on hormone levels and sperm count in adulthood. J Urol. 1999;162(3 Pt 2):986–8; discussion 989.PubMedGoogle Scholar
  80. 80.
    Longui CA, Arnhold IJ, Mendonca BB, et al. Serum inhibin levels before and after gonadotropin stimulation in cryptorchid boys under age 4 years. J Pediatr Endocrinol Metab. 1998;11(6):687–92.PubMedCrossRefGoogle Scholar
  81. 81.
    De Muinck Keizer-Schrama SM, Hazebroek FW. Hormonal treatment of cryptorchidism: role of pituitary gonadal axis. Semin Urol. 1988;6(2):84–95.PubMedGoogle Scholar
  82. 82.
    Raivio T, Dunkel L. Inverse relationship between serum inhibin B and FSH levels in prepubertal boys with cryptorchidism. Pediatr Res. 1999;46(5):496–500.PubMedCrossRefGoogle Scholar
  83. 83.
    Suomi AM, Main KM, Kaleva M, et al. Hormonal changes in 3-month-old cryptorchid boys. J Clin Endocrinol Metab. 2006;91(3):953–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Irkilata HC, Yildirim I, Onguru O, et al. The influence of orchiopexy on serum inhibin B level: relationship with histology. J Urol. 2004;172(6 Pt 1):2402–5; discussion 2405.PubMedCrossRefGoogle Scholar
  85. 85.
    Thorup J, Petersen BL, Kvist K, et al. Bilateral undescended testes classified according to preoperative and postoperative status of gonadotropins and inhibin B in relation to testicular histopathology at bilateral orchiopexy in infant boys. J Urol. 2012;188(4 Suppl):1436–42.PubMedCrossRefGoogle Scholar
  86. 86.
    Thorup J, Clasen-Linde E, Thorup SC, et al. Pre- and postoperative status of gonadotropins (FSH and LH) and inhibin-B in relation to testicular histopathology at orchiopexy in infant boys with unilateral undescended testes. J Pediatr Urol. 2014;11(1):25 e1–5.Google Scholar
  87. 87.
    Andersson AM, Petersen JH, Jorgensen N, et al. Serum inhibin B and follicle-stimulating hormone levels as tools in the evaluation of infertile men: significance of adequate reference values from proven fertile men. J Clin Endocrinol Metab. 2004;89(6):2873–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Cortes D, Thorup J, Lindenberg S, et al. Infertility despite surgery for cryptorchidism in childhood can be classified by patients with normal or elevated follicle-stimulating hormone and identified at orchidopexy. BJU Int. 2003;91(7):670–4.PubMedCrossRefGoogle Scholar
  89. 89.
    Thorup J, Kvist K, Clasen-Linde E, et al. The relation between adult dark spermatogonia and other parameters of fertility potential in cryptorchid testes. J Urol. 2013;190(4 Suppl):1566–71.PubMedCrossRefGoogle Scholar
  90. 90.
    Fenichel P, Lahlou N, Coquillard P, et al. Cord blood Insulin-like peptide 3 (INSL3) but not testosterone is reduced in idiopathic cryptorchidism. Clin Endocrinol (Oxf). 2015;82(2):242–7.CrossRefGoogle Scholar
  91. 91.
    Biggs ML, Baer A, Critchlow CW. Maternal, delivery, and perinatal characteristics associated with cryptorchidism: a population-based case-control study among births in Washington State. Epidemiology. 2002;13(2):197–204.PubMedCrossRefGoogle Scholar
  92. 92.
    Chedane C, Puissant H, Weil D, et al. Association between altered placental human chorionic gonadotrophin (hCG) production and the occurrence of cryptorchidism: a retrospective study. BMC Pediatr. 2014;14:191.PubMedCentralPubMedCrossRefGoogle Scholar
  93. 93.
    Weidner IS, Moller H, Jensen TK, et al. Risk factors for cryptorchidism and hypospadias. J Urol. 1999;161(5):1606–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Sekaran P, O’Toole S, Flett M, et al. Increased occurrence of disorders of sex development, prematurity and intrauterine growth restriction in children with proximal hypospadias associated with undescended testes. J Urol. 2013;189(5):1892–6.PubMedCrossRefGoogle Scholar
  95. 95.
    Jensen MS, Toft G, Thulstrup AM, et al. Cryptorchidism concordance in monozygotic and dizygotic twin brothers, full brothers, and half-brothers. Fertil Steril. 2010;93(1):124–9.PubMedCrossRefGoogle Scholar
  96. 96.
    Schnack TH, Zdravkovic S, Myrup C, et al. Familial aggregation of cryptorchidism – a nationwide cohort study. Am J Epidemiol. 2008;167(12):1453–7.PubMedCrossRefGoogle Scholar
  97. 97.
    Czeizel A, Erodi E, Toth J. Genetics of undescended testis. J Urol. 1981;126(4):528–9.PubMedGoogle Scholar
  98. 98.
    Jones IR, Young ID. Familial incidence of cryptorchidism. J Urol. 1982;127(3):508–9.PubMedGoogle Scholar
  99. 99.
    Elert A, Jahn K, Heidenreich A, et al. The familial undescended testis. Klin Padiatr. 2003;215(1):40–5.PubMedCrossRefGoogle Scholar
  100. 100.
    Hemminki K, Li X, Sundquist K, et al. Familial risks for common diseases: etiologic clues and guidance to gene identification. Mutat Res. 2008;658(3):247–58.PubMedCrossRefGoogle Scholar
  101. 101.
    Ferlin A, Zuccarello D, Garolla A, et al. Mutations in INSL3 and RXFP2 genes in cryptorchid boys. Ann N Y Acad Sci. 2009;1160:213–4.PubMedCrossRefGoogle Scholar
  102. 102.
    Bertini V, Bertelloni S, Valetto A, et al. Homeobox HOXA10 gene analysis in cryptorchidism. J Pediatr Endocrinol Metab. 2004;17(1):41–5.PubMedCrossRefGoogle Scholar
  103. 103.
    Kolon TF, Wiener JS, Lewitton M, et al. Analysis of homeobox gene HOXA10 mutations in cryptorchidism. J Urol. 1999;161(1):275–80.PubMedCrossRefGoogle Scholar
  104. 104.
    Wang Y, Barthold J, Kanetsky PA, et al. Allelic variants in HOX genes in cryptorchidism. Birth Defects Res A Clin Mol Teratol. 2007;79(4):269–75.PubMedCrossRefGoogle Scholar
  105. 105.
    Galan JJ, Guarducci E, Nuti F, et al. Molecular analysis of estrogen receptor alpha gene AGATA haplotype and SNP12 in European populations: potential protective effect for cryptorchidism and lack of association with male infertility. Hum Reprod. 2007;22(2):444–9.PubMedCrossRefGoogle Scholar
  106. 106.
    Lo Giacco D, Ars E, Bassas L, et al. ESR1 promoter polymorphism is not associated with nonsyndromic cryptorchidism. Fertil Steril. 2011;95(1):369–71, 371 e1-2.PubMedCrossRefGoogle Scholar
  107. 107.
    Wang Y, Barthold J, Figueroa E, et al. Analysis of five single nucleotide polymorphisms in the ESR1 gene in cryptorchidism. Birth Defects Res A Clin Mol Teratol. 2008;82(6):482–5.PubMedCrossRefGoogle Scholar
  108. 108.
    Yoshida R, Fukami M, Sasagawa I, et al. Association of cryptorchidism with a specific haplotype of the estrogen receptor alpha gene: implication for the susceptibility to estrogenic environmental endocrine disruptors. J Clin Endocrinol Metab. 2005;90(8):4716–21.PubMedCrossRefGoogle Scholar
  109. 109.
    Davis-Dao C, Koh CJ, Hardy BE, et al. Shorter androgen receptor CAG repeat lengths associated with cryptorchidism risk among Hispanic white boys. J Clin Endocrinol Metab. 2012;97(3):E393–9.PubMedCrossRefGoogle Scholar
  110. 110.
    Ferlin A, Garolla A, Bettella A, et al. Androgen receptor gene CAG and GGC repeat lengths in cryptorchidism. Eur J Endocrinol. 2005;152(3):419–25.PubMedCrossRefGoogle Scholar
  111. 111.
    Radpour R, Rezaee M, Tavasoly A, et al. Association of long polyglycine tracts (GGN repeats) in exon 1 of the androgen receptor gene with cryptorchidism and penile hypospadias in Iranian patients. J Androl. 2007;28(1):164–9.PubMedCrossRefGoogle Scholar
  112. 112.
    Sasagawa I, Suzuki Y, Tateno T, et al. CAG repeat length of the androgen receptor gene in Japanese males with cryptorchidism. Mol Hum Reprod. 2000;6(11):973–5.PubMedCrossRefGoogle Scholar
  113. 113.
    Silva-Ramos M, Oliveira JM, Cabeda JM, et al. The CAG repeat within the androgen receptor gene and its relationship to cryptorchidism. Int Braz J Urol. 2006;32(3):330–4; discussion 335.PubMedCrossRefGoogle Scholar
  114. 114.
    Qin XY, Kojima Y, Mizuno K, et al. Association of variants in genes involved in environmental chemical metabolism and risk of cryptorchidism and hypospadias. J Hum Genet. 2012;57(7):434–41.PubMedCrossRefGoogle Scholar
  115. 115.
    Wada Y, Okada M, Fukami M, et al. Association of cryptorchidism with Gly146Ala polymorphism in the gene for steroidogenic factor-1. Fertil Steril. 2006;85(3):787–90.PubMedCrossRefGoogle Scholar
  116. 116.
    Dalgaard MD, Weinhold N, Edsgard D, et al. A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation. J Med Genet. 2012;49(1):58–65.PubMedCentralPubMedCrossRefGoogle Scholar
  117. 117.
    Sarraj MA, Escalona RM, Umbers A, et al. Fetal testis dysgenesis and compromised Leydig cell function in Tgfbr3 (beta glycan) knockout mice. Biol Reprod. 2010;82(1):153–62.PubMedCrossRefGoogle Scholar
  118. 118.
    Virtanen HE, Adamsson A. Cryptorchidism and endocrine disrupting chemicals. Mol Cell Endocrinol. 2012;355(2):208–20.PubMedCrossRefGoogle Scholar
  119. 119.
    Zhao X, Onteru S, Saatchi M, et al. A genome-wide association study for canine cryptorchidism in Siberian Huskies. J Anim Breed Genet. 2014;131(3):202–9.PubMedCrossRefGoogle Scholar
  120. 120.
    Skakkebaek NE, Rajpert-De ME, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001;16(5):972–8.PubMedCrossRefGoogle Scholar
  121. 121.
    Rantakokko P, Main KM, Wohlfart-Veje C, et al. Association of placenta organotin concentrations with congenital cryptorchidism and reproductive hormone levels in 280 newborn boys from Denmark and Finland. Hum Reprod. 2013;28(6):1647–60.PubMedCrossRefGoogle Scholar
  122. 122.
    Koskenniemi JJ, Virtanen HE, Kiviranta H. Association between levels of persistent organic pollutants in adipose tissue and cryptorchidism in early childhood: a case-control study. Environ Health. 2015;14:78.Google Scholar
  123. 123.
    Furst P. Dioxins, polychlorinated biphenyls and other organohalogen compounds in human milk. Levels, correlations, trends and exposure through breastfeeding. Mol Nutr Food Res. 2006;50(10):922–33.PubMedCrossRefGoogle Scholar
  124. 124.
    Thomsen C, Stigum H, Froshaug M, et al. Determinants of brominated flame retardants in breast milk from a large scale Norwegian study. Environ Int. 2010;36(1):68–74.PubMedCrossRefGoogle Scholar
  125. 125.
    Patandin S, Dagnelie PC, Mulder PG, et al. Dietary exposure to polychlorinated biphenyls and dioxins from infancy until adulthood: a comparison between breast-feeding, toddler, and long-term exposure. Environ Health Perspect. 1999;107(1):45–51.PubMedCentralPubMedCrossRefGoogle Scholar
  126. 126.
    Kiviranta H, Ovaskainen ML, Vartiainen T. Market basket study on dietary intake of PCDD/Fs, PCBs, and PBDEs in Finland. Environ Int. 2004;30(7):923–32.PubMedCrossRefGoogle Scholar
  127. 127.
    Schecter A, Papke O, Harris TR, et al. Polybrominated diphenyl ether (PBDE) levels in an expanded market basket survey of U.S. food and estimated PBDE dietary intake by age and sex. Environ Health Perspect. 2006;114(10):1515–20.PubMedCentralPubMedCrossRefGoogle Scholar
  128. 128.
    de Wit CA, Bjorklund JA, Thuresson K. Tri-decabrominated diphenyl ethers and hexabromocyclododecane in indoor air and dust from Stockholm microenvironments 2: indoor sources and human exposure. Environ Int. 2012;39(1):141–7.PubMedCrossRefGoogle Scholar
  129. 129.
    Brucker-Davis F, Wagner-Mahler K, Delattre I, et al. Cryptorchidism at birth in Nice area (France) is associated with higher prenatal exposure to PCBs and DDE, as assessed by colostrum concentrations. Hum Reprod. 2008;23(8):1708–18.PubMedCrossRefGoogle Scholar
  130. 130.
    Main KM, Kiviranta H, Virtanen HE, et al. Flame retardants in placenta and breast milk and cryptorchidism in newborn boys. Environ Health Perspect. 2007;115(10):1519–26.PubMedCentralPubMedGoogle Scholar
  131. 131.
    Krysiak-Baltyn K, Toppari J, Skakkebaek NE, et al. Association between chemical pattern in breast milk and congenital cryptorchidism: modelling of complex human exposures. Int J Androl. 2012;35(3):294–302.PubMedCrossRefGoogle Scholar
  132. 132.
    McGlynn KA, Guo X, Graubard BI, et al. Maternal pregnancy levels of polychlorinated biphenyls and risk of hypospadias and cryptorchidism in male offspring. Environ Health Perspect. 2009;117(9):1472–6.PubMedCentralPubMedCrossRefGoogle Scholar
  133. 133.
    Mol NM, Sorensen N, Weihe P, et al. Spermaturia and serum hormone concentrations at the age of puberty in boys prenatally exposed to polychlorinated biphenyls. Eur J Endocrinol. 2002;146(3):357–63.PubMedCrossRefGoogle Scholar
  134. 134.
    Hosie S, Loff S, Witt K, et al. Is there a correlation between organochlorine compounds and undescended testes? Eur J Pediatr Surg. 2000;10(5):304–9.PubMedCrossRefGoogle Scholar
  135. 135.
    Garcia-Rodriguez J, Garcia-Martin M, Nogueras-Ocana M, et al. Exposure to pesticides and cryptorchidism: geographical evidence of a possible association. Environ Health Perspect. 1996;104(10):1090–5.PubMedCentralPubMedCrossRefGoogle Scholar
  136. 136.
    Andersen HR, Schmidt IM, Grandjean P, et al. Impaired reproductive development in sons of women occupationally exposed to pesticides during pregnancy. Environ Health Perspect. 2008;116(4):566–72.PubMedCentralPubMedCrossRefGoogle Scholar
  137. 137.
    Hakonsen LB, Ernst A, Ramlau-Hansen CH. Maternal cigarette smoking during pregnancy and reproductive health in children: a review of epidemiological studies. Asian J Androl. 2014;16(1):39–49.PubMedCentralPubMedCrossRefGoogle Scholar
  138. 138.
    Hackshaw A, Rodeck C, Boniface S. Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls. Hum Reprod Update. 2011;17(5):589–604.PubMedCentralPubMedCrossRefGoogle Scholar
  139. 139.
    Varvarigou AA, Liatsis SG, Vassilakos P, et al. Effect of maternal smoking on cord blood estriol, placental lactogen, chorionic gonadotropin, FSH, LH, and cortisol. J Perinat Med. 2009;37(4):364–9.PubMedGoogle Scholar
  140. 140.
    Zhang L, Wang XH, Zheng XM, et al. Maternal gestational smoking, diabetes, alcohol drinking, pre-pregnancy obesity and the risk of cryptorchidism: a systematic review and meta-analysis of observational studies. PLoS One. 2015;10(3):e0119006.PubMedCentralPubMedCrossRefGoogle Scholar
  141. 141.
    Kristensen DM, Hass U, Lesne L, et al. Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat. Hum Reprod. 2011;26(1):235–44.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • John M. Hutson
    • 1
  • Jørgen M. Thorup
    • 2
  • Spencer W. Beasley
    • 3
  1. 1.Royal Children’s Hospital University of MelbourneParkvilleAustralia
  2. 2.Univ. Hospital of Copenhagen RigshospitaletKøbenhavnDenmark
  3. 3.University of OtagoChristchurchNew Zealand

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