Possible fetal determinants of male infertility

Nature Reviews Endocrinology

Volumn 10, Issue 9, 2014, Pages 553-562

  Juul, Anders ^a   Almstrup, Kristian ^a   Andersson, Anna Maria ^a   Jensen, Tina K ^a   Jørgensen, Niels ^a   Main, Katharina M ^a   Meyts, Ewa Rajpert De ^a   Toppari, Jorma ^a   Skakkebæk, Niels E ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ENDOCRINE DISRUPTOR; TESTOSTERONE;

ALCOHOL CONSUMPTION; DISEASE SEVERITY; DISORDER OF SEX DEVELOPMENT; ENVIRONMENTAL EXPOSURE; FETUS DEVELOPMENT; GENE MUTATION; GONADAL DYSGENESIS; HISTOPATHOLOGY; HUMAN; KARYOTYPE 46,XY; LEYDIG CELL; LIFESTYLE; MALE INFERTILITY; MATERNAL SMOKING; OBESITY; PRIORITY JOURNAL; REVIEW; SEMEN ANALYSIS; SERTOLI CELL ONLY SYNDROME; SEX TRANSFORMATION; SPERMATOGENESIS; SYMPTOMATOLOGY; TESTIS CANCER;

ANIMALS; DISORDERS OF SEX DEVELOPMENT; ENDOCRINE DISRUPTORS; FEMALE; FETAL GROWTH RETARDATION; HUMANS; INFERTILITY, MALE; KLINEFELTER SYNDROME; MALE; MOTHERS; PREGNANCY; PRENATAL EXPOSURE DELAYED EFFECTS; SMOKING; TESTICULAR NEOPLASMS; TESTIS; TESTOSTERONE;

EID: 84906790795     PISSN: 17595029     EISSN: 17595037     Source Type: Journal    
DOI: 10.1038/nrendo.2014.97     Document Type: Review

References (140)

1. Skakkebæk, N. E., Rajpert-De Meyts, E. & Main, K. M. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum. Reprod. 16, 972-978 (2001). (Pubitemid 32451837)
2. Mocarelli, P. et al. Dioxin exposure, from infancy through puberty, produces endocrine disruption and affects human semen quality. Environ. Health Perspect. 116, 70-77 (2008).
3. Klinefelter, H. F., Reifenstein, E. C. & Albright, F. Syndrome characterised by gynecomastia, aspermatogenesis, with A-Leydigism and increased excretion of follicle stimulating hormone. J. Clin. Endocrinol. 2, 615-627 (1942).
4. Aksglæde, L., Skakkebæk, N. E., Almstrup, K. & Juul, A. Clinical and biological parameters in 166 boys, adolescents and adults with nonmosaic Klinefelter syndrome: a Copenhagen experience. Acta Paediatr. 100, 793-806 (2011).
5. Isidor, B. et al. Familial frameshift SRY mutation inherited from a mosaic father with testicular dysgenesis syndrome. J. Clin. Endocrinol. Metab. 94, 3467-3471 (2009).
6. Lottrup, G. et al. Identification of a novel androgen receptor mutation in a family with multiple components compatible with the testicular dysgenesis syndrome. J. Clin. Endocrinol. Metab. 98, 2223-2229 (2013).
7. Lindhardt Johansen, M. et al. 45,X/46,XY mosaicism: phenotypic characteristics, growth, and reproductive function-a retrospective longitudinal study. J. Clin. Endocrinol. Metab. 97, E1540-E1549 (2012).
8. Jacobs, P. A. & Strong, J. A. A case of human intersexuality having a possible XXY sex-determining mechanism. Nature 183, 302-303 (1959).
9. Dayangac, D. et al. Mutations of the CFTR gene in Turkish patients with congenital bilateral absence of the vas deferens. Hum. Reprod. 19, 1094-1100 (2004). (Pubitemid 38618488)
10. Priskorn, L. et al. Increasing trends in childlessness in recent birth cohorts-a registry-based study of the total Danish male population born from 1945 to 1980. Int. J. Androl. 35, 449-455 (2012).
11. Louis, J. F. et al. The prevalence of couple infertility in the United States from a male perspective: evidence from a nationally representative sample. Andrology 1, 741-748 (2013).
12. Schmidt, L., Münster, K. & Helm, P. Infertility and the seeking of infertility treatment in a representative population. Br. J. Obstet. Gynaecol. 102, 978-984 (1995). (Pubitemid 26014993)
13. Schmidt, L. Infertility and assisted reproduction in Denmark. Epidemiology and psychosocial consequences. Dan. Med. Bull. 53, 390-417 (2006). (Pubitemid 44822012)
14. Zegers-Hochschild, F. et al. The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary on ART terminology, 2009. Hum. Reprod. 24, 2683-2687 (2009).
15. Andersen, A. N. & Erb, K. Register data on assisted reproductive technology (ART) in Europe including a detailed description of ART in Denmark. Int. J. Androl. 29, 12-16 (2006).
16. Danish Fertility Society. Annual report 2013 [online], http://www.fertilitetsselskab.dk/(2014).
17. Jain, T. & Gupta, R. S. Trends in the use of intracytoplasmic sperm injection in the United States. N. Engl. J. Med. 357, 251-257 (2007). (Pubitemid 47080389)
18. WHO. WHO laboratory manual for the examination and processing of human semen [online], http://whqlibdoc.who.int/publications/2010/9789241547789eng.pdf (2010).
19. Guzick, D. S. et al. Sperm morphology, motility, and concentration in fertile and infertile men. N. Engl. J. Med. 345, 1388-1393 (2001).
20. Bonde, J. P. E. et al. Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners. Lancet 352, 1172-1177 (1998). (Pubitemid 28458531)
21. Slama, R. et al. Time to pregnancy and semen parameters: a cross-sectional study among fertile couples from four European cities. Hum. Reprod. 17, 503-515 (2002). (Pubitemid 34168467)
22. Sharpe, R. M. & Skakkebæk, N. E. Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects. Fertil. Steril. 89 (Suppl. 2), e33-e38 (2008). (Pubitemid 351749385)
23. Welsh, M. et al. Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism. J. Clin. Invest. 118, 1479-1490 (2008). (Pubitemid 351500441)
24. The Organization for Economic Co-operation and Development. OECD guideline for testing of chemicals. Reproduction/developmental toxicity screening test [online], http://www.oecd-ilibrary.org/docserver/download/ 9742101e.pdf?expires=1401272715&id=id&accname=guest&checksum= BE06CE9598F68D8220F28D9065C2CDB4 (1995).
25. Veeramachaneni, D. N., Palmer, J. S., Amann, R. P. & Pau, K. Y. Sequelae in male rabbits following developmental exposure to p,p'-DDT or a mixture of p,p'-DDT and vinclozolin: cryptorchidism, germ cell atypia, and sexual dysfunction. Reprod. Toxicol. 23, 353-365 (2007). (Pubitemid 46602935)
26. Veeramachaneni, D. N., Amann, R. P. & Jacobson, J. P. Testis and antler dysgenesis in sitka black-tailed deer on Kodiak Island, Alaska: sequela of environmental endocrine disruption? Environ. Health Perspect. 114 (Suppl. 1), 51-59 (2006).
27. Bay, K., Main, K. M., Toppari, J. & Skakkebæk, N. E. Testicular descent: INSL 3, testosterone, genes and the intrauterine milieu. Nat. Rev. Urol. 8, 187-196 (2011).
28. Swaab, D. F. Sexual differentiation of the brain and behavior. Best Pract. Res. Clin. Endocrinol. Metab. 21, 431-444 (2007). (Pubitemid 47387101)
29. Rajpert-De Meyts, E. Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects. Hum. Reprod. Update 12, 303-323 (2006).
30. Looijenga, L. H. J., de Munnik, H. & Oosterhuis, J. W. A molecular model for the development of germ cell cancer. Int. J. Cancer 83, 809-814 (1999).
31. Rørth, M. et al. Carcinoma in situ in the testis. Scand. J. Urol. Nephrol. 205, 166-186 (2000). (Pubitemid 32056472)
32. Skakkebæk, N. E., Berthelsen, J. G., Giwercman, A. & Müller, J. Carcinoma-in-situ of the testis: possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma. Int. J. Androl. 10, 19-28 (1987). (Pubitemid 17081837)
33. Almstrup, K. et al. Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling. Cancer Res. 64, 4736-4743 (2004). (Pubitemid 38924515)
34. Skakkebæk, N. E. Carcinoma in situ of the testis: frequency and relationship to invasive germ cell tumours in infertile men. Histopathology 2, 157-170 (1978). (Pubitemid 8357412)
35. Bergström, R. et al. Increase in testicular cancer incidence in six European countries: a birth cohort phenomenon. J. Natl Cancer Inst. 88, 727-733 (1996). (Pubitemid 26195020)
36. Møller, H. Clues to the aetiology of testicular germ cell tumours from descriptive epidemiology. Eur. Urol. 23, 8-15 (1993). (Pubitemid 23103454)
37. Müller, J., Skakkebæk, N. E., Ritzén, E. M., Plöen, L. & Petersen, K. E. Carcinoma in situ of the testis in children with 45,X/46,XY gonadal dysgenesis. J. Pediatr. 106, 431-436 (1985).
38. Müller, J., Visfeldt, J. & Skakkebæk, N. E. Gonadoblastoma and invasive neoplasia in 2 girls with 46,XY gonadal dysgenesis. Horm. Res. 33 (Suppl. 3), 57 (1990).
39. Looijenga, L. H. et al. POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors. Cancer Res. 63, 2244-2250 (2003). (Pubitemid 36538633)
40. Cools, M. et al. Gonadal pathology and tumor risk in relation to clinical characteristics in patients with 45,X/46,XY mosaicism. J. Clin. Endocrinol. Metab. 96, E1171-E1180 (2011).
41. Abdullah, N. A. et al. Birth prevalence of cryptorchidism and hypospadias in Northern England, 1993-2000. Arch. Dis. Child. 92, 576-579 (2007). (Pubitemid 47012947)
42. Jaffray, B., Moore, L. & Dickson, A. P. Prader-Willi syndrome and intratubular germ cell neoplasia. Med. Pediatr. Oncol. 32, 73-74 (1999). (Pubitemid 29029348)
43. Berthelsen, J. G. & Skakkebæk, N. E. Gonadal function in men with testis cancer. Fertil. Steril. 39, 68-75 (1983). (Pubitemid 13224246)
44. Berthelsen, J. G. Andrological aspects of testicular cancer. Int. J. Androl. 7, 451-483 (1984). (Pubitemid 15160111)
45. Petersen, P. M., Skakkebæk, N. E., Vistisen, K., Rørth, M. & Giwercman, A. Semen quality and reproductive hormones before orchiectomy in men with testicular cancer. J. Clin. Oncol. 17, 941-947 (1999). (Pubitemid 29109327)
46. Walsh, T. J., Croughan, M. S., Schembri, M., Chan, J. M. & Turek, P. J. Increased risk of testicular germ cell cancer among infertile men. Arch. Intern. Med. 169, 351-356 (2009).
47. Møller, H. & Skakkebaek, N. E. Risk of testicular cancer in subfertile men: case-control study. Br. Med. J. 318, 559-562 (1999). (Pubitemid 29188952)
48. Akre, O. & Richiardi, L. Does a testicular dysgenesis syndrome exist? Hum. Reprod. 24, 2053-2060 (2009).
49. Asklund, C. et al. Semen quality, reproductive hormones and fertility of men operated for hypospadias. Int. J. Androl. 33, 80-87 (2010).
50. Schnack, T. H., Poulsen, G., Myrup, C., Wohlfahrt, J. & Melbye, M. Familial coaggregation of cryptorchidism, hypospadias, and testicular germ cell cancer: a nationwide cohort study. J. Natl Cancer Inst. 102, 187-192 (2009).
51. Cools, M. & Looijenga, L. H. Tumor risk and clinical follow-up in patients with disorders of sex development. Pediatr. Endocrinol. Rev. 9 (Suppl. 1), 519-524 (2011).
52. Rud, C. N. et al. Sperm concentration, testicular volume and age predict risk of carcinoma-in-situ in contralateral testis of men with testicular germ-cell cancer. J. Urol. 190, 2074-2080 (2013).
53. Olesen, I. A. et al. Testicular carcinoma in situ in subfertile Danish men. Int. J. Androl. 30, 406-412 (2007).
54. Høi-Hansen, C. E., Holm, M., Rajpert-De Meyts, E. & Skakkebæk, N. E. Histological evidence of testicular dysgenesis in contralateral biopsies from 218 patients with testicular germ cell cancer. J. Pathol. 200, 370-374 (2003). (Pubitemid 36827311)
55. Yong, E. L., Loy, C. J. & Sim, K. S. Androgen receptor gene and male infertility. Hum. Reprod. Update 18, 1-7 (2003). (Pubitemid 36305579)
56. Ferlin, A., Arredi, B. & Foresta, C. Genetic causes of male infertility. Reprod. Toxicol. 30, 133-141 (2006). (Pubitemid 43994384)
57. Hellmann, P. et al. Male patients with partial androgen insensitivity syndrome: a longitudinal follow-up of growth, reproductive hormones and the development of gynaecomastia. Arch. Dis. Child. 97, 403-409 (2012).
58. Aksglæde, L. et al. Natural history of seminiferous tubule degeneration in Klinefelter syndrome. Hum. Reprod. Update 12, 39-48 (2006). (Pubitemid 43013745)
59. Skakkebæk, N. E. Two types of tubules containing only Sertoli cells in adults with Klinefelter's syndrome. Nature 223, 643-645 (1969).
60. McLachlan, R. I., Rajpert-De Meyts, E., Høi-Hansen, C. E., De Kretser, D. M. & Skakkebæk, N. E. Histological evaluation of the human testis-approaches to optimizing the clinical value of the assessment: mini review. Hum. Reprod. 22, 2-16 (2007). (Pubitemid 44942661)
61. Mehta, A., Paduch, D. A. & Schlegel, P. N. Successful testicular sperm retrieval in adolescents with Klinefelter syndrome treated with at least 1 year of topical testosterone and aromatase inhibitor. Fertil. Steril. 100, e27 (2013).
62. Vorona, E., Zitzmann, M., Gromoll, J., Schuring, A. N. & Nieschlag, E. Clinical, endocrinological, and epigenetic features of the 46,XX male syndrome, compared with 47,XXY Klinefelter patients. J. Clin. Endocrinol. Metab. 21, 3458-3465 (2007). (Pubitemid 47435320)
63. Ottesen, A. M. et al. Increased number of sex chromosomes affects height in a nonlinear fashion: a study of 305 patients with sex chromosome aneuploidy. Am. J. Med. Genet. A 152A, 1206-1212 (2010).
64. Leppig, K. A. & Disteche, C. M. Ring X and other structural X chromosome abnormalities: X inactivation and phenotype. Semin. Reprod. Med. 19, 147-157 (2001). (Pubitemid 32847029)
65. Richardson, M. E., Bleiziffer, A., Tuttelmann, F., Gromoll, J. & Wilkinson, M. F. Epigenetic regulation of the RHOX homeobox gene cluster and its association with human male infertility. Hum. Mol. Genet. 23, 12-23 (2014).
66. Le Cornet, C. et al. Testicular cancer incidence to rise by 25% by 2025 in Europe? Model-based predictions in 40 countries using population-based registry data. Eur. J. Cancer 50, 831-839 (2014).
67. Main, K. M., Jensen, R. B., Asklund, C., Høi-Hansen, C. E. & Skakkebæk, N. E. Low birth weight and male reproductive function. Horm. Res. 65 (Suppl. 3), 116-122 (2006). (Pubitemid 44689443)
68. Nordenvall, A. S., Frisen, L., Nordenstrom, A., Lichtenstein, P. & Nordenskjold, A. A population-based nationwide study of hypospadias in Sweden, 1973-2009: incidence and risk factors. J. Urol. 191, 783-789 (2013).
69. Virtanen, H. E. & Toppari, J. Epidemiology and pathogenesis of cryptorchidism. Hum. Reprod. Update 14, 49-58 (2008).
70. Depue, R. H., Pike, M. C. & Henderson, B. E. Birth weight and the risk of testicular cancer. J. Natl Cancer Inst. 77, 829-830 (1986).
71. Møller, H. & Skakkebæk, N. E. Testicular cancer and cryptorchidism in relation to prenatal factors: case-control studies in Denmark. Cancer Causes Control 8, 904-912 (1997). (Pubitemid 27485466)
72. Francois, I., De Zegher, F., Spiessens, C., D'Hooge, T. & Vanderschueren, D. Low birth weight and subsequent male subfertility. Pediatr. Res. 42, 899-901 (1997).
73. Cicognani, A. et al. Low birth weight for gestational age and subsequent male gonadal function. J. Pediatr. 141, 376-380 (2002).
74. Vanbillemont, G. et al. Birth weight in relation to sex steroid status and body composition in young healthy male siblings. J. Clin. Endocrinol. Metab. 95, 1587-1594 (2010).
75. Jensen, R. B. et al. Pituitary-gonadal function in adolescent males born appropriate or small for gestational age with or without intrauterine growth restriction. J. Clin. Endocrinol. Metab. 92, 1353-1357 (2007). (Pubitemid 46556409)
76. Kerkhof, G. F. et al. Influence of preterm birth and birth size on gonadal function in young men. J. Clin. Endocrinol. Metab. 94, 4243-4250 (2009).
77. Damgaard, I. N. et al. Risk factors for congenital cryptorchidism in a prospective birth cohort study. PLoS ONE. 3, e3051 (2008).
78. Virtanen, H. E. et al. Mild gestational diabetes as a risk factor for congenital cryptorchidism. J. Clin. Endocrinol. Metab. 91, 4862-4865 (2006). (Pubitemid 44917319)
79. van Rooij, I. A. et al. Risk factors for different phenotypes of hypospadias: results from a Dutch case-control study. BJU Int. 112, 121-128 (2013).
80. Carmichael, S. L. et al. Hypospadias and maternal intake of phytoestrogens. Am. J. Epidemiol. 178, 434-440 (2013).
81. Thorup, J., Cortes, D. & Petersen, B. L. 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. 176, 734-737 (2006). (Pubitemid 43927906)
82. Ravnborg, T. L. et al. Prenatal and adult exposures to smoking are associated with adverse effects on reproductive hormones, semen quality, final height and body mass index. Hum. Reprod. 26, 1000-1011 (2011).
83. Ratcliffe, J. M., Gladen, B. C., Wilcox, A. J. & Herbst, A. L. Does early exposure to maternal smoking affect future fertility in adult males? Reprod. Toxicol. 6, 297-307 (1992).
84. Jensen, T. K. et al. Adult and prenatal exposures to tobacco smoke as risk indicators of fertility among 430 Danish couples. Am. J. Epidemiol. 148, 992-997 (1998). (Pubitemid 28533739)
85. Storgaard, L. et al. Does smoking during pregnancy affect sons' sperm counts? Epidemiology 14, 278-286 (2003). (Pubitemid 40417078)
86. Jensen, T. K. et al. Association of in utero exposure to maternal smoking with reduced semen quality and testis size in adulthood: a cross-sectional study of 1,770 young men from the general population in five European countries. Am. J. Epidemiol. 159, 49-58 (2004).
87. Ramlau-Hansen, C. H. et al. Maternal smoking in pregnancy and reproductive hormones in adult sons. Int. J. Androl. 31, 565-572 (2008).
88. Toppari, J. et al. Male reproductive health and environmental xenoestrogens. Environ. Health Perspect. 104, 741-803 (1996). (Pubitemid 26290302)
89. MacLeod, D. J. et al. Androgen action in the masculinization programming window and development of male reproductive organs. Int. J. Androl. 33, 279-287 (2010).
90. Fisher, J. S., Macpherson, S., Marchetti, N. & Sharpe, R. M. Human "testicular dysgenesis syndrome": a possible model using in-utero exposure of the rat to dibutyl phthalate. Hum. Reprod. 18, 1383-1394 (2003). (Pubitemid 36840943)
91. Hass, U. et al. Combined exposure to anti-androgens exacerbates disruption of sexual differentiation in the rat. Environ. Health Perspect. 115 (Suppl. 1), 122-128 (2007).
92. Hardell, L. et al. Increased concentrations of polychlorinated biphenyls, hexachlorobenzene, and chlordanes in mothers of men with testicular cancer. Environ. Health Perspect. 111, 930-934 (2003). (Pubitemid 36790388)
93. Krysiak-Baltyn, K. et al. Country-specific chemical signatures of persistent environmental compounds in breast milk. Int. J. Androl. 33, 270-278 (2010).
94. Kortenkamp, A. Ten years of mixing cocktails: a review of combination effects of endocrine-disrupting chemicals. Environ. Health Perspect. 115 (Suppl. 1), 98-105 (2007).
95. Orton, F., Rosivatz, E., Scholze, M. & Kortenkamp, A. Widely used pesticides with previously unknown endocrine activity revealed as in vitro antiandrogens. Environ. Health Perspect. 119, 794-800 (2011).
96. Kristensen, D. M. et al. Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat. Hum. Reprod. 26, 235-244 (2011).
97. Mazaud-Guittot, S. et al. Paracetamol, aspirin, and indomethacin induce endocrine disturbances in the human fetal testis capable of interfering with testicular descent. J. Clin. Endocrinol. Metab. 98, E1757-E1767 (2013).
98. Snijder, C. A. et al. Intrauterine exposure to mild analgesics during pregnancy and the occurrence of cryptorchidism and hypospadia in the offspring: the Generation R Study. Hum. Reprod. 27, 1191-1201 (2012).
99. Jensen, M. S. et al. Analgesics during pregnancy and cryptorchidism: additional analyses. Epidemiology 22, 610-612 (2011).
100. Andersen, H. R. et al. Impaired reproductive development in sons of women occupationally exposed to pesticides during pregnancy. Environ. Health Perspect. 116, 566-572 (2008). (Pubitemid 351864320)
101. Wohlfahrt-Veje, C. et al. Smaller genitals at school age in boys whose mothers were exposed to non-persistent pesticides in early pregnancy. Int. J. Androl. 35, 265-272 (2012).
102. Chul, K. S., Kyoung, K. S. & Pyo, H. Y. Trends in the incidence of cryptorchidism and hypospadias of registry-based data in Korea: a comparison between industrialized areas of petrochemical estates and a non-industrialized area. Asian J. Androl. 13, 715-718 (2011).
103. Krysiak-Baltyn, K. et al. Association between chemical pattern in breast milk and congenital cryptorchidism: modelling of complex human exposures. Int. J. Androl. 35, 294-302 (2012).
104. Rantakokko, P. et al. Association of placenta organotin concentrations with congenital cryptorchidism and reproductive hormone levels in 280 newborn boys from Denmark and Finland. Hum. Reprod. 28, 1647-1660 (2013).
105. Virtanen, H. E. et al. Associations between congenital cryptorchidism in newborn boys and levels of dioxins and PCBs in placenta. Int. J. Androl. 35, 283-293 (2012).
106. Main, K. M. et al. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in three months old infants. Environ. Health Perspect. 114, 270-276 (2006). (Pubitemid 43193651)
107. Damgaard, I. N. et al. Persistent pesticides in human breast milk and cryptorchidism. Environ. Health Perspect. 114, 1133-1138 (2006). (Pubitemid 44018912)
108. Main, K. M. et al. Flame retardants in placenta and breast milk and cryptorchidism in newborn boys. Environ. Health Perspect. 115, 1519-1526 (2007). (Pubitemid 47618096)
109. Swan, S. H. et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ. Health Perspect. 113, 1056-1061 (2005). (Pubitemid 41149638)
110. Longnecker, M. P. et al. Maternal serum level of 1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene and risk of cryptorchidism, hypospadias, and polythelia among male offspring. Am. J. Epidemiol. 155, 313-322 (2002). (Pubitemid 34132049)
111. 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. 23, 1708-1718 (2008). (Pubitemid 352020015)
112. Pierik, F. H., Klebanoff, M. A., Brock, J. W. & Longnecker, M. P. Maternal pregnancy serum level of heptachlor epoxide, hexachlorobenzene, and β-hexachlorocyclohexane and risk of cryptorchidism in offspring. Environ. Res. 105, 364-369 (2007). (Pubitemid 47542262)
113. van der Zanden, L. F. et al. Exploration of gene-environment interactions, maternal effects and parent of origin effects in the etiology of hypospadias. J. Urol. 188, 2354-2360 (2012).
114. Qin, X. Y. et al. Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients. PLoS ONE 7, e52756 (2012).
115. Andersen, H. R. et al. Paraoxonase-1 polymorphism and prenatal pesticide exposure associated with adverse cardiovascular risk profiles at school age. PLoS ONE 7, e36830 (2012).
116. Joensen, U. N. et al. Associations of filaggrin gene loss-of-function variants with urinary phthalate metabolites and testicular function in young Danish men. Environ. Health Perspect. 122, 345-350 (2014).
117. Swan, S. H. Prenatal phthalate exposure and anogenital distance in male infants. Environ. Health Perspect. 114, A88-A89 (2006). (Pubitemid 43193606)
118. Thankamony, A. et al. Anogenital distance and penile length in infants with hypospadias or cryptorchidism: comparison with normative data. Environ. Health Perspect. 122, 207-211 (2014).
119. Hsieh, M. H., Breyer, B. N., Eisenberg, M. L. & Baskin, L. S. Associations among hypospadias, cryptorchidism, anogenital distance, and endocrine disruption. Curr. Urol. Rep. 9, 137-142 (2008). (Pubitemid 351480794)
120. Gray, L. E. Jr et al. Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals. Int. J. Androl. 29, 96-104 (2006).
121. Scott, H. M. et al. Relationship between androgen action in the "male programming window," fetal Sertoli cell number, and adult testis size in the rat. Endocrinology 149, 5280-5287 (2008).
122. Suzuki, Y., Yoshinaga, J., Mizumoto, Y., Serizawa, S. & Shiraishi, H. Foetal exposure to phthalate esters and anogenital distance in male newborns. Int. J. Androl. 35, 236-244 (2012).
123. Miao, M. et al. In utero exposure to bisphenol-A and anogenital distance of male offspring. Birth Defects Res. A Clin. Mol. Teratol. 91, 867-872 (2011).
124. Hotchkiss, A. K. et al. A mixture of the "antiandrogens" linuron and butyl benzyl phthalate alters sexual differentiation of the male rat in a cumulative fashion. Biol. Reprod. 71, 1852-1861 (2004). (Pubitemid 39586929)
125. Mendiola, J., Stahlhut, R. W., Jørgensen, N., Liu, F. & Swan, S. H. Shorter anogenital distance predicts poorer semen quality in young men in Rochester, New York. Environ. Health Perspect. 119, 958-963 (2011).
126. Eisenberg, M. L., Hsieh, M. H., Walters, R. C., Krasnow, R. & Lipshultz, L. I. The relationship between anogenital distance, fatherhood, and fertility in adult men. PLoS ONE 6, e18973 (2011).
127. Eisenberg, M. L., Jensen, T. K., Walters, R. C., Skakkebæk, N. E. & Lipshultz, L. I. The relationship between anogenital distance and reproductive hormone levels in adult men. J. Urol. 187, 594-598 (2012).
128. Eisenberg, M. L., Shy, M., Walters, R. C. & Lipshultz, L. I. The relationship between anogenital distance and azoospermia in adult men. Int. J. Androl. 35, 726-730 (2012).
129. Travison, T. G., Araujo, A. B., O'Donnell, A. B., Kupelian, V. & McKinlay, J. B. A population-level decline in serum testosterone levels in American men. J. Clin. Endocrinol. Metab. 92, 196-202 (2007). (Pubitemid 46075010)
130. Andersson, A. M. et al. Secular decline in male testosterone and sex hormone binding globulin serum levels in Danish population surveys. J. Clin. Endocrinol. Metab. 92, 4696-4705 (2007).
131. Perheentupa, A. et al. A cohort effect on serum testosterone levels in Finnish men. Eur. J. Endocrinol. 168, 227-233 (2013).
132. Jørgensen, N. et al. Human semen quality in the new millennium: a prospective cross-sectional population-based study of 4,867 men. BMJ Open 2, e000990 (2012).
133. Aksglæde, L. et al. Primary testicular failure in Klinefelter's syndrome: the use of bivariate luteinizing hormone-testosterone reference charts. Clin. Endocrinol. 66, 276-281 (2007). (Pubitemid 46096149)
134. Andersson, A. M., Jørgensen, N., Larsen, L. F., Rajpert-De Meyts, E. & Skakkebæk, N. E. Impaired Leydig cell function in infertile men: a study of 357 idiopathic infertile men and 318 proven fertile controls. J. Clin. Endocrinol. Metab. 89, 3161-3167 (2004). (Pubitemid 38951879)
135. Gracia, J., Zalabardo, J. S., Garcia, J. S., Garcia, C. & Ferrandez, A. Clinical, physical, sperm and hormonal data in 251 adults operated on for cryptorchidism in childhood. BJU Int. 85, 1100-1103 (2000). (Pubitemid 30348808)
136. Werder, E. A. et al. Gonadal function in young adults after surgical treatment of cryptorchidism. Br. Med. J. 2, 1357-1359 (1976).
137. Blanc, T. et al. Testicular function and physical outcome in young adult males diagnosed with idiopathic 46 XY disorders of sex development during childhood. Eur. J. Endocrinol. 165, 907-915 (2011).
138. Suomi, A.-M. et al. Hormonal changes in 3-month-old cryptorchid boys. J. Clin. Endocrinol. Metab. 91, 953-958 (2006). (Pubitemid 43357764)
139. Pierik, F. H. et al. The hypothalamus-pituitary-testis axis in boys during the first six months of life: a comparison of cryptorchidism and hypospadias cases with controls. Int. J. Androl. 32, 453-461 (2008).
140. Sathyanarayana, S., Beard, L., Zhou, C. & Grady, R. Measurement and correlates of ano-genital distance in healthy, newborn infants. Int. J. Androl. 33, 317-323 (2010).