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Cryptorchidism and Hypospadias

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Health Impacts of Developmental Exposure to Environmental Chemicals

Abstract

Several pieces of evidence indicated the effect of environmental chemicals on the prevalence of cryptorchidism and hypospadias. In addition, several other factors, such as genetic factors, gene mutations, endocrinopathies, also cause cryptorchidism and hypospadias. From reviewing papers in this chapter, the evidence for these associations remains controversial; hence, there are not adequate data to establish an association between exposure to environmental chemicals and cryptorchidism or hypospadias. On the other hand, genes and polymorphisms involved in metabolism of environmental endocrine disruptors might influence the risk of male genital malformations. Thus, further cohort studies are required.

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Abbreviations

AHRs:

Aromatic hydrocarbon receptors

ARNT2:

Aryl hydrocarbon receptor nuclear translocator 2

BPA:

Bisphenol A

CGRP:

Calcitonin gene-related peptide

DES:

Diethylstilbestrol

DGKK:

Diacylglycerol kinase κ

DLCs:

Dioxin-like compounds

EDCs:

Endocrine-disrupting chemicals

EEDs:

Environmental endocrine disruptors

ESR:

Estrogen receptor

HCB:

Hexachlorobenzene

HCE:

Heptachlor epoxide

HOX:

Homeobox

INSL3:

Insulin-like factor 3

NTSR1:

Neurotensin receptor 1

OCPs:

Organochlorine pesticides

PBDEs:

Polybrominated diphenyl ethers

PCBs:

Polychlorinated biphenyls

PFAAs:

Perfluoroalkyl acids

PFASs:

Perfluoroalkyl substances

PFOA:

Perfluorooctanoate

PFOS:

Perfluorooctane sulfonate

PRL:

Prolactin

TDS:

Testicular dysgenesis syndrome

References

  1. Skakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001;16(5):972–8.

    Article  CAS  PubMed  Google Scholar 

  2. Wohlfahrt-Veje C, Main KM, Skakkebaek NE. Testicular dysgenesis syndrome: foetal origin of adult reproductive problems. Clin Endocrinol. 2009;71(4):459–65.

    Article  Google Scholar 

  3. Shih EM, Graham JM Jr. Review of genetic and environmental factors leading to hypospadias. Eur J Med Genet. 2014;57(8):453–63.

    Article  PubMed  Google Scholar 

  4. van der Zanden LF, et al. Aetiology of hypospadias: a systematic review of genes and environment. Hum Reprod Update. 2012;18(3):260–83.

    Article  PubMed  CAS  Google Scholar 

  5. Sijstermans K, et al. The frequency of undescended testis from birth to adulthood: a review. Int J Androl. 2008;31(1):1–11.

    CAS  PubMed  Google Scholar 

  6. Lane C, et al. A population-based study of prevalence trends and geospatial analysis of hypospadias and cryptorchidism compared with non-endocrine mediated congenital anomalies. J Pediatr Urol. 2017;13(3):284.e1–7.

    Article  Google Scholar 

  7. Abdullah NA, et al. Birth prevalence of cryptorchidism and hypospadias in northern England, 1993-2000. Arch Dis Child. 2007;92(7):576–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ritzen EM, et al. Nordic consensus on treatment of undescended testes. Acta Paediatr. 2007;96(5):638–43.

    Article  PubMed  Google Scholar 

  9. Trsinar B, Muravec UR. Fertility potential after unilateral and bilateral orchidopexy for cryptorchidism. World J Urol. 2009;27(4):513–9.

    Article  PubMed  Google Scholar 

  10. Hutson JM. A biphasic model for the hormonal control of testicular descent. Lancet. 1985;2(8452):419–21.

    Article  CAS  PubMed  Google Scholar 

  11. Hutson JM, et al. Regulation of testicular descent. Pediatr Surg Int. 2015;31(4):317–25.

    Article  PubMed  Google Scholar 

  12. Favorito LA, et al. The importance of the gubernaculum in testicular migration during the human fetal period. Int Braz J Urol. 2014;40(6):722–9.

    Article  PubMed  Google Scholar 

  13. Levard G, Laberge JM. The fate of undescended testes in patients with gastroschisis. Eur J Pediatr Surg. 1997;7(3):163–5.

    Article  CAS  PubMed  Google Scholar 

  14. Husmann DA, Levy JB. Current concepts in the pathophysiology of testicular undescent. Urology. 1995;46(2):267–76.

    Article  CAS  PubMed  Google Scholar 

  15. Shenker NS, et al. A new role for androgen in testicular descent: permitting gubernacular cell proliferation in response to the neuropeptide, calcitonin gene-related peptide. J Pediatr Surg. 2006;41(2):407–12.

    Article  PubMed  Google Scholar 

  16. Kurzrock EA, Baskin LS, Cunha GR. Ontogeny of the male urethra: theory of endodermal differentiation. Differentiation. 1999;64(2):115–22.

    Article  CAS  PubMed  Google Scholar 

  17. van der Werff JF, et al. Normal development of the male anterior urethra. Teratology. 2000;61(3):172–83.

    Article  PubMed  Google Scholar 

  18. Seifert AW, Harfe BD, Cohn MJ. Cell lineage analysis demonstrates an endodermal origin of the distal urethra and perineum. Dev Biol. 2008;318(1):143–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Baskin LS. Hypospadias and urethral development. J Urol. 2000;163(3):951–6.

    Article  CAS  PubMed  Google Scholar 

  20. Sagodi L, et al. Prevalence and possible causes of hypospadias. Orv Hetil. 2014;155(25):978–85.

    Article  PubMed  Google Scholar 

  21. Paulozzi LJ, Erickson JD, Jackson RJ. Hypospadias trends in two US surveillance systems. Pediatrics. 1997;100(5):831–4.

    Article  CAS  PubMed  Google Scholar 

  22. Paulozzi LJ. International trends in rates of hypospadias and cryptorchidism. Environ Health Perspect. 1999;107(4):297–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dolk H, et al. Toward the effective surveillance of hypospadias. Environ Health Perspect. 2004;112(3):398–402.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Yu X, et al. Hypospadias prevalence and trends in international birth defect surveillance systems, 1980-2010. Eur Urol. 2019;76:482–90.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wein AJ, et al. Hypospadias. Campbell-Walsh urology, vol. 4. 11th ed. Philadelphia: Elsevier; 2015. p. 3503–36.

    Google Scholar 

  26. Manson JM, Carr MC. Molecular epidemiology of hypospadias: review of genetic and environmental risk factors. Birth Defects Res A Clin Mol Teratol. 2003;67(10):825–36.

    Article  CAS  PubMed  Google Scholar 

  27. Manzoni G, et al. Hypospadias surgery: when, what and by whom? BJU Int. 2004;94(8):1188–95.

    Article  PubMed  Google Scholar 

  28. Haudid AT, Azmy AF. Hypospadias surgery. Berlin: Springer; 2004.

    Book  Google Scholar 

  29. Bingham SA, et al. Phyto-oestrogens: where are we now? Br J Nutr. 1998;79(5):393–406.

    Article  CAS  PubMed  Google Scholar 

  30. North K, Golding J. A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. BJU Int. 2000;85(1):107–13.

    Article  CAS  PubMed  Google Scholar 

  31. Brouwers MM, et al. Risk factors for hypospadias. Eur J Pediatr. 2007;166(7):671–8.

    Article  PubMed  Google Scholar 

  32. Akre O, et al. Maternal and gestational risk factors for hypospadias. Environ Health Perspect. 2008;116(8):1071–6.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Giordano F, et al. Maternal diet and the risk of hypospadias and cryptorchidism in the offspring. Paediatr Perinat Epidemiol. 2008;22(3):249–60.

    Article  PubMed  Google Scholar 

  34. Zhang L, 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Kurahashi N, et al. Parental and neonatal risk factors for cryptorchidism. Med Sci Monit. 2005;11(6):CR274–83.

    PubMed  Google Scholar 

  36. Brouwers MM, et al. Hypospadias: risk factor patterns and different phenotypes. BJU Int. 2010;105(2):254–62.

    Article  PubMed  Google Scholar 

  37. Hussain N, et al. Hypospadias and early gestation growth restriction in infants. Pediatrics. 2002;109(3):473–8.

    Article  PubMed  Google Scholar 

  38. Meyer KJ, et al. Agricultural pesticide use and hypospadias in eastern Arkansas. Environ Health Perspect. 2006;114(10):1589–95.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Strandberg-Larsen K, et al. Alcohol binge drinking during pregnancy and cryptorchidism. Hum Reprod. 2009;24(12):3211–9.

    Article  CAS  PubMed  Google Scholar 

  40. Kavlock RJ, et al. Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop. Environ Health Perspect. 1996;104(Suppl 4):715–40.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Diamanti-Kandarakis E, et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev. 2009;30(4):293–342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lymperi S, Giwercman A. Endocrine disruptors and testicular function. Metabolism. 2018;86:79–90.

    Article  CAS  PubMed  Google Scholar 

  43. Desdoits-Lethimonier C, et al. Human testis steroidogenesis is inhibited by phthalates. Hum Reprod. 2012;27(5):1451–9.

    Article  CAS  PubMed  Google Scholar 

  44. Main KM, et al. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environ Health Perspect. 2006;114(2):270–6.

    Article  CAS  PubMed  Google Scholar 

  45. Jensen MS, et al. Amniotic fluid phthalate levels and male fetal gonad function. Epidemiology. 2015;26(1):91–9.

    Article  PubMed  Google Scholar 

  46. Pan G, et al. Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China. Environ Health Perspect. 2006;114(11):1643–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mendiola J, et al. Associations between urinary metabolites of di(2-ethylhexyl) phthalate and reproductive hormones in fertile men. Int J Androl. 2011;34(4):369–78.

    Article  CAS  PubMed  Google Scholar 

  48. Meeker JD, Calafat AM, Hauser R. Urinary metabolites of di(2-ethylhexyl) phthalate are associated with decreased steroid hormone levels in adult men. J Androl. 2009;30(3):287–97.

    Article  CAS  PubMed  Google Scholar 

  49. Araki A, et al. Association between maternal exposure to di(2-ethylhexyl) phthalate and reproductive hormone levels in fetal blood: the Hokkaido study on environment and children's health. PLoS One. 2014;9(10):e109039.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Araki A, et al. Prenatal di(2-ethylhexyl) phthalate exposure and disruption of adrenal androgens and glucocorticoids levels in cord blood: The Hokkaido Study. Sci Total Environ. 2017;581-582:297–304.

    Article  CAS  PubMed  Google Scholar 

  51. Wagner-Mahler K, et al. Prospective study on the prevalence and associated risk factors of cryptorchidism in 6246 newborn boys from Nice area, France. Int J Androl. 2011;34(5 Pt 2):e499–510.

    Article  CAS  PubMed  Google Scholar 

  52. Swan SH. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environ Res. 2008;108(2):177–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ormond G, et al. Endocrine disruptors in the workplace, hair spray, folate supplementation, and risk of hypospadias: case-control study. Environ Health Perspect. 2009;117(2):303–7.

    Article  PubMed  Google Scholar 

  54. Carran M, Shaw IC. New Zealand Malayan war veterans’ exposure to dibutylphthalate is associated with an increased incidence of cryptorchidism, hypospadias and breast cancer in their children. N Z Med J. 2012;125(1358):52–63.

    PubMed  Google Scholar 

  55. Chevrier C, et al. Maternal urinary phthalates and phenols and male genital anomalies. Epidemiology. 2012;23(2):353–6.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Vrijheid M, et al. Risk of hypospadias in relation to maternal occupational exposure to potential endocrine disrupting chemicals. Occup Environ Med. 2003;60(8):543–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Nassar N, et al. Parental occupational exposure to potential endocrine disrupting chemicals and risk of hypospadias in infants. Occup Environ Med. 2010;67(9):585–9.

    Article  CAS  PubMed  Google Scholar 

  58. Warembourg C, et al. Exposure of pregnant women to persistent organic pollutants and cord sex hormone levels. Hum Reprod. 2016;31(1):190–8.

    Article  CAS  PubMed  Google Scholar 

  59. Araki A, et al. Prenatal organochlorine pesticide exposure and the disruption of steroids and reproductive hormones in cord blood: The Hokkaido Study. Environ Int. 2018;110:1–13.

    Article  CAS  PubMed  Google Scholar 

  60. Gabel P, et al. The risk of cryptorchidism among sons of women working in horticulture in Denmark: a cohort study. Environ Health. 2011;10:100.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Jorgensen KT, et al. Risk of cryptorchidism among sons of horticultural workers and farmers in Denmark. Scand J Work Environ Health. 2014;40(3):323–30.

    Article  PubMed  Google Scholar 

  62. Weidner IS, et al. Cryptorchidism and hypospadias in sons of gardeners and farmers. Environ Health Perspect. 1998;106(12):793–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Damgaard IN, et al. Persistent pesticides in human breast milk and cryptorchidism. Environ Health Perspect. 2006;114(7):1133–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Hosie S, et al. Is there a correlation between organochlorine compounds and undescended testes? Eur J Pediatr Surg. 2000;10(5):304–9.

    Article  CAS  PubMed  Google Scholar 

  65. Kristensen P, et al. Birth defects among offspring of Norwegian farmers, 1967-1991. Epidemiology. 1997;8(5):537–44.

    Article  CAS  PubMed  Google Scholar 

  66. Carbone P, et al. The possible role of endocrine disrupting chemicals in the aetiology of cryptorchidism and hypospadias: a population-based case-control study in rural Sicily. Int J Androl. 2007;30(1):3–13.

    Article  CAS  PubMed  Google Scholar 

  67. 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.

    Article  PubMed  Google Scholar 

  68. Carmichael SL, et al. Hypospadias and residential proximity to pesticide applications. Pediatrics. 2013;132(5):e1216–26.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Trabert B, et al. Maternal pregnancy levels of trans-nonachlor and oxychlordane and prevalence of cryptorchidism and hypospadias in boys. Environ Health Perspect. 2012;120(3):478–82.

    Article  CAS  PubMed  Google Scholar 

  70. Vandenberg LN, et al. Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr Rev. 2009;30(1):75–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Galloway T, et al. Daily bisphenol A excretion and associations with sex hormone concentrations: results from the InCHIANTI adult population study. Environ Health Perspect. 2010;118(11):1603–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Minatoya M, et al. Cord blood bisphenol A levels and reproductive and thyroid hormone levels of neonates: The Hokkaido Study on Environment and Children’s Health. Epidemiology. 2017;28(Suppl 1):S3–9.

    Article  PubMed  Google Scholar 

  73. Choi H, et al. The association between some endocrine disruptors and hypospadias in biological samples. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2012;47(13):2173–9.

    Article  CAS  PubMed  Google Scholar 

  74. Fernandez MF, et al. Bisphenol A and other phenols in human placenta from children with cryptorchidism or hypospadias. Reprod Toxicol. 2016;59:89–95.

    Article  CAS  PubMed  Google Scholar 

  75. Chevalier N, et al. A negative correlation between insulin-like peptide 3 and bisphenol A in human cord blood suggests an effect of endocrine disruptors on testicular descent during fetal development. Hum Reprod. 2015;30(2):447–53.

    Article  CAS  PubMed  Google Scholar 

  76. Van den Berg M, et al. The 2005 World Health Organization reevaluation of human and Mammalian toxic equivalency factors for dioxins and dioxin-like compounds. Toxicol Sci. 2006;93(2):223–41.

    Article  PubMed  CAS  Google Scholar 

  77. Hsu PC, et al. Serum hormones in boys prenatally exposed to polychlorinated biphenyls and dibenzofurans. J Toxicol Environ Health A. 2005;68(17-18):1447–56.

    Article  CAS  PubMed  Google Scholar 

  78. Cao Y, et al. Environmental exposure to dioxins and polychlorinated biphenyls reduce levels of gonadal hormones in newborns: results from the Duisburg cohort study. Int J Hyg Environ Health. 2008;211(1-2):30–9.

    Article  CAS  PubMed  Google Scholar 

  79. Miyashita C, et al. Sex-related differences in the associations between maternal dioxin-like compounds and reproductive and steroid hormones in cord blood: The Hokkaido Study. Environ Int. 2018;117:175–85.

    Article  CAS  PubMed  Google Scholar 

  80. Brucker-Davis F, 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.

    Article  CAS  PubMed  Google Scholar 

  81. Main KM, et al. Flame retardants in placenta and breast milk and cryptorchidism in newborn boys. Environ Health Perspect. 2007;115(10):1519–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. McGlynn KA, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Carmichael SL, et al. Hypospadias and halogenated organic pollutant levels in maternal mid-pregnancy serum samples. Chemosphere. 2010;80(6):641–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Lopez-Espinosa MJ, et al. Perfluoroalkyl substances, sex hormones, and insulin-like growth factor-1 at 6-9 years of age: a cross-sectional analysis within the C8 health project. Environ Health Perspect. 2016;124(8):1269–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Vested A, et al. Associations of in utero exposure to perfluorinated alkyl acids with human semen quality and reproductive hormones in adult men. Environ Health Perspect. 2013;121(4):453–8.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Goudarzi H, et al. The association of prenatal exposure to perfluorinated chemicals with glucocorticoid and androgenic hormones in cord blood samples: The Hokkaido Study. Environ Health Perspect. 2016;125:111–8.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Itoh S, et al. Association of perfluoroalkyl substances exposure in utero with reproductive hormone levels in cord blood in the Hokkaido Study on Environment and Children’s Health. Environ Int. 2016;94:51–9.

    Article  CAS  PubMed  Google Scholar 

  88. Vesterholm Jensen D, et al. No association between exposure to perfluorinated compounds and congenital cryptorchidism: a nested case-control study among 215 boys from Denmark and Finland. Reproduction. 2014;147(4):411–7.

    Article  PubMed  CAS  Google Scholar 

  89. Aschim EL, et al. Linkage between cryptorchidism, hypospadias, and GGN repeat length in the androgen receptor gene. J Clin Endocrinol Metab. 2004;89(10):5105–9.

    Article  CAS  PubMed  Google Scholar 

  90. Radpour R, 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.

    Article  CAS  PubMed  Google Scholar 

  91. Ferlin A, et al. Androgen receptor gene CAG and GGC repeat lengths in cryptorchidism. Eur J Endocrinol. 2005;152(3):419–25.

    Article  CAS  PubMed  Google Scholar 

  92. Wang Q, et al. Association of androgen receptor gene CAG and GGN repeat polymorphism with cryptorchidism: a meta-analysis. Andrologia. 2018;50(3):12909.

    Article  CAS  Google Scholar 

  93. Wiener JS, et al. Androgen receptor gene alterations are not associated with isolated cryptorchidism. J Urol. 1998;160(3 Pt 1):863–5.

    Article  CAS  PubMed  Google Scholar 

  94. Lo Giacco D, et al. ESR1 promoter polymorphism is not associated with nonsyndromic cryptorchidism. Fertil Steril. 2011;95(1):369–71.

    Article  CAS  PubMed  Google Scholar 

  95. Wang Y, 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.

    Article  CAS  PubMed  Google Scholar 

  96. Beleza-Meireles A, et al. Polymorphisms of estrogen receptor beta gene are associated with hypospadias. J Endocrinol Investig. 2006;29(1):5–10.

    Article  CAS  Google Scholar 

  97. Choudhry S, et al. Genetic polymorphisms in ESR1 and ESR2 genes, and risk of hypospadias in a multiethnic study population. J Urol. 2015;193(5):1625–31.

    Article  CAS  PubMed  Google Scholar 

  98. Ban S, et al. Genetic polymorphisms of ESR1 and ESR2 that may influence estrogen activity and the risk of hypospadias. Hum Reprod. 2008;23(6):1466–71.

    Article  CAS  PubMed  Google Scholar 

  99. Watanabe M, et al. Haplotype analysis of the estrogen receptor 1 gene in male genital and reproductive abnormalities. Hum Reprod. 2007;22(5):1279–84.

    Article  CAS  PubMed  Google Scholar 

  100. Chavez-Saldana M, et al. Single nucleotide polymorphisms associated with nonsyndromic cryptorchidism in Mexican patients. Andrologia. 2018;50(1):12788.

    Article  CAS  Google Scholar 

  101. Takahashi I, et al. Ala/Thr60 variant of the Leydig insulin-like hormone is not associated with cryptorchidism in the Japanese population. Pediatr Int. 2001;43(3):256–8.

    Article  CAS  PubMed  Google Scholar 

  102. Baker LA, et al. The insulin-3 gene: lack of a genetic basis for human cryptorchidism. J Urol. 2002;167(6):2534–7.

    Article  CAS  PubMed  Google Scholar 

  103. Kolon TF, et al. Analysis of homeobox gene HOXA10 mutations in cryptorchidism. J Urol. 1999;161(1):275–80.

    Article  CAS  PubMed  Google Scholar 

  104. Lu P, et al. Genetic analysis of HOXA11 gene in Chinese patients with cryptorchidism. Andrologia. 2018;50(1):12790.

    Article  CAS  Google Scholar 

  105. Wang Y, et al. Allelic variants in HOX genes in cryptorchidism. Birth Defects Res A Clin Mol Teratol. 2007;79(4):269–75.

    Article  CAS  PubMed  Google Scholar 

  106. Ars E, et al. Further insights into the role of T222P variant of RXFP2 in non-syndromic cryptorchidism in two Mediterranean populations. Int J Androl. 2011;34(4):333–8.

    Article  CAS  PubMed  Google Scholar 

  107. Zhou B, et al. The variations in the AXIN1 gene and susceptibility to cryptorchidism. J Pediatr Urol. 2015;11(3):132 e1–5.

    Article  Google Scholar 

  108. Ma Q, et al. Diacylglycerol kinase kappa (DGKK) variants and hypospadias in Han Chinese: association and meta-analysis. BJU Int. 2015;116(4):634–40.

    Article  CAS  PubMed  Google Scholar 

  109. Zhang K, et al. Steroid 5-alpha-reductase type 2 (SRD5A2) gene V89L polymorphism and hypospadias risk: a meta-analysis. J Pediatr Urol. 2017;13(6):630 e1–9.

    Article  Google Scholar 

  110. Samtani R, et al. Hypospadias risk and polymorphism in SRD5A2 and CYP17 genes: case-control study among Indian children. J Urol. 2011;185(6):2334–9.

    Article  CAS  PubMed  Google Scholar 

  111. Kojima Y, et al. Single nucleotide polymorphisms of HAAO and IRX6 genes as risk factors for hypospadias. J Urol. 2019;201(2):386–92.

    Article  PubMed  Google Scholar 

  112. Kalfa N, et al. Genomic variants of ATF3 in patients with hypospadias. J Urol. 2008;180(5):2183–8.

    Article  CAS  PubMed  Google Scholar 

  113. Beleza-Meireles A, et al. Activating transcription factor 3: a hormone responsive gene in the etiology of hypospadias. Eur J Endocrinol. 2008;158(5):729–39.

    Article  CAS  PubMed  Google Scholar 

  114. Fukami M, et al. CXorf6 is a causative gene for hypospadias. Nat Genet. 2006;38(12):1369–71.

    Article  CAS  PubMed  Google Scholar 

  115. Ogata T, Fukami M, Wada Y. MAMLD1 (CXorf6) is a new gene for hypospadias. Clin Pediatr Endocrinol. 2008;17(4):87–93.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Chen Y, et al. Mutational study of the MAMLD1-gene in hypospadias. Eur J Med Genet. 2010;53(3):122–6.

    Article  PubMed  Google Scholar 

  117. Kalfa N, et al. Mutations of CXorf6 are associated with a range of severities of hypospadias. Eur J Endocrinol. 2008;159(4):453–8.

    Article  CAS  PubMed  Google Scholar 

  118. Ohsako S, et al. Expression of xenobiotic biomarkers CYP1 family in preputial tissue of patients with hypospadias and phimosis and its association with DNA methylation level of SRD5A2 minimal promoter. Arch Environ Contam Toxicol. 2018;74(2):240–7.

    Article  CAS  PubMed  Google Scholar 

  119. Kurahashi N, et al. Maternal genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 and the risk of hypospadias. Mol Hum Reprod. 2005;11(2):93–8.

    Article  CAS  PubMed  Google Scholar 

  120. Qin XY, et al. Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients. PLoS One. 2012;7(12):e52756.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Qin XY, 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.

    Article  CAS  PubMed  Google Scholar 

  122. Carmichael SL, et al. Joint effects of genetic variants and residential proximity to pesticide applications on hypospadias risk. Birth Defects Res A Clin Mol Teratol. 2016;106(8):653–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Kalfa N, et al. Is hypospadias associated with prenatal exposure to endocrine disruptors? A French Collaborative Controlled Study of a cohort of 300 consecutive children without genetic defect. Eur Urol. 2015;68(6):1023–30.

    Article  PubMed  Google Scholar 

  124. Suzuki Y, et al. Screening for mutations of the androgen receptor gene in patients with isolated cryptorchidism. Fertil Steril. 2001;76(4):834–6.

    Article  CAS  PubMed  Google Scholar 

  125. Thai HT, et al. The valine allele of the V89L polymorphism in the 5-alpha-reductase gene confers a reduced risk for hypospadias. J Clin Endocrinol Metab. 2005;90(12):6695–8.

    Article  CAS  PubMed  Google Scholar 

  126. Sata F, et al. Genetic polymorphisms of 17 beta-hydroxysteroid dehydrogenase 3 and the risk of hypospadias. J Sex Med. 2010;7(8):2729–38.

    Article  CAS  PubMed  Google Scholar 

  127. Kalfa N, et al. Polymorphisms of MAMLD1 gene in hypospadias. J Pediatr Urol. 2011;7(6):585–91.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, Graduate School of Medical Sciences, University of Yamanashi, Chuo, Yamanashi, Japan

    Takahiko Mitsui

  2. Health Center, Chuo University, Tokyo, Japan

    Fumihiro Sata

  3. Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Hokkaido, Japan

    Reiko Kishi

Authors
  1. Takahiko Mitsui
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  2. Fumihiro Sata
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  3. Reiko Kishi
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Correspondence to Takahiko Mitsui .

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Editors and Affiliations

  1. Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Hokkaido, Japan

    Reiko Kishi

  2. Department of Environmental Health Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Philippe Grandjean

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Mitsui, T., Sata, F., Kishi, R. (2020). Cryptorchidism and Hypospadias. In: Kishi, R., Grandjean, P. (eds) Health Impacts of Developmental Exposure to Environmental Chemicals. Current Topics in Environmental Health and Preventive Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-15-0520-1_4

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  • DOI: https://doi.org/10.1007/978-981-15-0520-1_4

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