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Developmental Exposure to Endocrine Disruptors and Male Urogenital Tract Malformations

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Endocrine Disruptors and Puberty

Part of the book series: Contemporary Endocrinology ((COE))

Abstract

Discrepancies in adverse trends in male reproductive health around the world are due in part to the difficulty of comparing studies from different time periods with distinct study populations and varied clinical definitions and diagnostic criteria for these processes. In this context, the apparent increase in the incidence of cryptorchidism and hypospadias in the Western world over recent decades, with a leveling off in hypospadias incidence in most European countries during the 1980s, can be questioned due to differences in case definitions, age at diagnosis, examination techniques, and study populations, e.g., registry versus cohort studies. Experimental investigations have supported the hypothesis of a link between environmental factors and urogenital tract malformations, suggesting that cryptorchidism and hypospadias are associated with exposure to environmental chemicals, especially those identified as endocrine-disrupting chemicals (EDCs). Exposure to EDCs during pregnancy may play a role in the development of male sexual disorders because sexual differentiation and reproductive functioning are critically dependent on the ratio of androgens to estrogens, and an imbalance in this ratio may be responsible for male congenital anomalies. Epidemiology studies have also indicated a link between EDCs and malformations. The accumulated evidence appears sufficient to endorse a precautionary approach, with the implementation of measures to reduce community exposure to EDCs, especially in women of childbearing age, both before and during pregnancy.

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References

  1. Skakkebæk 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  PubMed  Google Scholar 

  2. Itoh N, Kayama F, Tatsuki J, Tsukamoto T. Have sperm counts deteriorated over the past 20 years in healthy, young Japanese men? Results from the Sapporo area. J Androl. 2001;22:40–4.

    PubMed  CAS  Google Scholar 

  3. Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean P, Guillette Jr LJ, et al. Male reproductive health and environmental xenoestrogens. Environ Health Perspect. 1996;104:741–803.

    PubMed  CAS  Google Scholar 

  4. Akre O, Lipworth L, Cnattingius S, Sparen P, Ekbom A. Risk factor patterns for cryptorchidism and hypospadias. Epidemiology. 1999;10(4):364–9.

    Article  PubMed  CAS  Google Scholar 

  5. Weidner IS, Moller H, Jensen TK, Skakkebaek N. Cryptorchidism and hypospadias in sons of gardeners and farmers. Environ Health Perspect. 1998;106:793–6.

    Article  PubMed  CAS  Google Scholar 

  6. Boisen KA, Kaleva M, Main KM, Virtanen HE, Haavisto A-M, Schmidt IM, et al. Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet. 2004;363:1264–9.

    Article  PubMed  CAS  Google Scholar 

  7. Lund L, Engebjerg MC, Pedersen L, Ehrenstein V, Nørgaard M, Sørensen HT. Prevalence of hypospadias in Danish boys: a longitudinal study, 1977–2005. Eur Urol. 2009;55(5):1022–6.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  CAS  Google Scholar 

  10. Martinez-Frias ML, Prieto D, Prieto L, Bermejo E, Rodriguez-Pinilla E, Cuevas L. Secular decreasing trend of the frequency of hypospadias among newborn male infants in Spain. Birth Defects Res A Clin Mol Teratol. 2004;70:75–81.

    Article  PubMed  CAS  Google Scholar 

  11. Virtanen HE, Toppari J. Epidemiology and pathogenesis of cryptorchidism. Hum Reprod Update. 2008;14(1):49–58.

    Article  PubMed  CAS  Google Scholar 

  12. Acerini CL, Miles HL, Dunger DB, Ong KK, Hughes IA. The descriptive epidemiology of congenital and acquired cryptorchidism in a UK infant cohort. Arch Dis Child. 2009;94:868–72.

    Article  PubMed  CAS  Google Scholar 

  13. Preiksa RT, Zilaitien B, Matulevicius V, Skakkebaek NE, Petersen JH, Jorgensen N, 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;20:1928–32.

    Article  PubMed  CAS  Google Scholar 

  14. Boisen KA, Chellakooty M, Schmidt IM, Kai CM, Damgaard IN, Suomi AM, et al. Hypospadias in a cohort of 1072 Danish newborn boys: prevalence and relationship to placental weight, anthropometrical measurements at birth, and reproductive hormone levels at 3 months of age. J Clin Endocrinol Metab. 2005;90:4041–6.

    Article  PubMed  CAS  Google Scholar 

  15. Colborn T, Clement C. Wingspread consensus statement. Chemically induced alterations in sexual, functional development: the wildlife/human connection. Princeton: Princeton Scientific; 1992. p. 1–8.

    Google Scholar 

  16. Porta M, Puigdomènech E, Ballester F, Selva J, Ribas-Fitó N, Domínguez-Boada L, et al. Studies conducted in Spain on concentrations in humans of persistent toxic compounds. Gac Sanit. 2008;22(3):248–66. Review.

    Article  PubMed  Google Scholar 

  17. Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Olea-Serrano MF. The E-Screen as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environ Health Perspect. 1995;103:113–22.

    PubMed  CAS  Google Scholar 

  18. Gray LE, Ostby J, Monosson E, Klece WR. Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual differentiation of the male rat. Toxicol Ind Health. 1999;15:48–64.

    Article  PubMed  Google Scholar 

  19. Sohoni P, Sumpter JP. Several environmental oestrogens are also antiandrogens. J Endocrinol. 1998;158:327–39.

    Article  PubMed  CAS  Google Scholar 

  20. Sultan C, Balaguer P, Terouanne B, Georget V, Paris F, Jeandel C, et al. Environmental xenoestrogens, antiandrogens and disorders of male sexual differentiation. Mol Cell Endocrinol. 2001;178:99–105.

    Article  PubMed  CAS  Google Scholar 

  21. Olea N, Olea-Serrano F, Lardelli-Claret P, Rivas A, Barba-Navarro A. Inadvertent exposure to xenoestrogens in children. Toxicol Ind Health. 1999;15:151–8.

    Article  PubMed  CAS  Google Scholar 

  22. Dolk H, Vrijheid M. The impact of environmental pollution on congenital anomalies. Br Med Bull. 2003;68:25–45.

    Article  PubMed  CAS  Google Scholar 

  23. Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect. 2005;113:1056–61.

    Article  PubMed  CAS  Google Scholar 

  24. Krimsky S. Hormonal chaos: the scientific and social origins of the environmental endocrine hypothesis. Baltimore: Johns Hopkins University; 2000.

    Google Scholar 

  25. Lopez-Espinosa MJ, Granada A, Carreno J, Salvatierra M, Olea-Serrano F, et al. Organochlorine pesticides in placentas from Southern Spain and some related factors. Placenta. 2007;28(7):631–8.

    Article  PubMed  CAS  Google Scholar 

  26. Christiansen S, Scholze M, Axelstad M, Boberg J, Kortenkamp A, Hass U. Combined exposure to anti-androgens causes markedly increased frequencies of hypospadias in the rat. Int J Androl. 2008;31(2):241–8.

    Article  PubMed  CAS  Google Scholar 

  27. Kortenkamp A. Low dose mixture effects of endocrine disrupters: implications for risk assessment and epidemiology. Int J Androl. 2008;31(2):233–40.

    Article  PubMed  CAS  Google Scholar 

  28. Almstrup K, Fernandez MF, Petersen JH, Olea N, Skakkebaek NE, Leffers H. Dual effects of phytoestrogens result in u-shaped dose-response curves. Environ Health Perspect. 2002;110:743–8.

    Article  PubMed  CAS  Google Scholar 

  29. Weltje L, vom Saal FS, Oehlmann J. Reproductive stimulation by low doses of xenoestrogens contrasts with the view of hormesis as an adaptive response. Hum Exp Toxicol. 2005;24:431–7.

    Article  PubMed  CAS  Google Scholar 

  30. Fernandez MF, Olmos B, Granada A, López-Espinosa MJ, Molina-Molina JM, Fernandez JM, et al. Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case-control study. Environ Health Perspect. 2007;115 Suppl 1:8–14.

    Article  PubMed  Google Scholar 

  31. Kristensen P, Irgens LM, Andersen A, Bye AS, Sundheim L. Birth defects among offspring of Norwegian farmers. Epidemiology. 1997;8:537–44.

    Article  PubMed  CAS  Google Scholar 

  32. Garcia AM, Flecher T, Benavides FG, Orts E. Parental agricultural work and selected congenital malformations. Am J Epidemiol. 1999;149:64–74.

    PubMed  CAS  Google Scholar 

  33. Rueda-Domingo MT, Lopez-Navarrete E, Nogueras-Ocaña M, Lardelli-Claret P. Factores de riesgo de criptorquidia. Gac Sanit. 2001;15:398–405.

    PubMed  CAS  Google Scholar 

  34. Carbone P, Giordano F, Nori F, Mantovani A, Taruscio D, Lauria L, et al. Cryptorchidism and hypospadias in the Sicilian district of Ragusa and the use of pesticides. Reprod Toxicol. 2006;22(1):8–12.

    Article  PubMed  CAS  Google Scholar 

  35. Carbone P, Giordano F, Nori F, Mantovani A, Taruscio D, Lauria L, 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  PubMed  CAS  Google Scholar 

  36. Andersen HR, Schmidt IM, Grandjean P, Jensen TK, Budtz-Jørgensen E, Kjaerstad MB, et al. Impaired reproductive development in sons of women occupationally exposed to pesticides during pregnancy. Environ Health Perspect. 2008;116(4):566–72.

    Article  PubMed  Google Scholar 

  37. Zhu JL, Hjollund NH, Andersen AM, Olsen J. Occupational exposure to pesticides and pregnancy outcomes in gardeners and farmers: a study within the Danish National Birth Cohort. J Occup Environ Med. 2006;48(4):347–52.

    Article  PubMed  Google Scholar 

  38. Irgens A, Kruger K, Skorve AH, Irgens LM. Birth defects and paternal occupational exposure. Hypotheses tested in a record linkage based data set. Acta Obstet Gynecol Scand. 2000;79:465–70.

    Article  PubMed  CAS  Google Scholar 

  39. Olshan AF, Teschke K, Baird PA. Paternal occupation and congenital anomalies in offspring. Am J Ind Med. 1991;20:447–75.

    Article  PubMed  CAS  Google Scholar 

  40. Garcia-Rodriguez J, Garcia-Martin M, Nogueras-Ocaña M, de Dios Luna-del-Castillo J, Espigares Garcia M, Olea N, et al. Exposure to pesticides and cryptorchidism: geographical evidence of a possible association. Environ Health Perspect. 1996;104:1090–5.

    PubMed  CAS  Google Scholar 

  41. Restrepo M, Muñoz N, Day N, Parra JE, Hernandez C, Blettner M, et al. Birth defects among children born to a population occupationally exposed to pesticides in Colombia. Scand J Work Environ Health. 1990;16:239–46.

    PubMed  CAS  Google Scholar 

  42. Pierik FH, Burdorf A, Deddens JA, Juttmann RE, Weber RFA. Maternal and paternal risk factors for cryptorchidism and hypospadias: a case-control study in newborn boys. Environ Health Perspect. 2004;112:1570–6.

    Article  PubMed  Google Scholar 

  43. Van Tongeren M, Nieuwenhuijsen MJ, Gardiner K, Armstrong B, Vrijheid M, Dolk H, et al. A job-exposure matrix for potential endocrine-disrupting chemicals developed for a study into the association between maternal occupation and hypospadias. Ann Occup Hyg. 2002;46:465–77.

    Article  PubMed  Google Scholar 

  44. Vrijheid M, Armstrong B, Dolk H, van Tongeren M, Botting B. Risk of hypospadias in relation to maternal occupational exposure to potential endocrine disrupting chemicals. Occup Environ Med. 2003;60:543–50.

    Article  PubMed  CAS  Google Scholar 

  45. Ormond G, Nieuwenhuijsen MJ, Nelson P, Toledano MB, Iszatt N, Geneletti S, 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.

    PubMed  Google Scholar 

  46. Dolk H, Vrijheid M, Armstrong B, Abramsky L, Bianchi F, Garne E, et al. Risk of congenital anomalies near hazardous-waste landfill sites in Europe: the EUROHAZCON study. Lancet. 1998;352:423–7.

    Article  PubMed  CAS  Google Scholar 

  47. Hosie S, Loff S, Witt K, Niessen K, Waag KL. Is there a correlation between organochlorine compounds and undescended testes? Eur J Pediatr Surg. 2000;10:304–9.

    Article  PubMed  CAS  Google Scholar 

  48. Longnecker MP, Klebanoff MA, Brock JW, Zhou H, Gray KA, Needham LL, 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. 2002;155:313–22.

    Article  PubMed  Google Scholar 

  49. Bhatia R, Shiau R, Petreas M, Weintraub JM, Farhang L, Eskenazi B. Organochlorine pesticides and male genital anomalies in the child health and development studies. Environ Health Perspect. 2005;113:220–4.

    Article  PubMed  CAS  Google Scholar 

  50. Damgaard IN, Skakkebaek NE, Toppari J, Virtanen HE, Shen H, Schramm KW, et al. Persistent pesticides in human breast milk and cryptorchidism. Environ Health Perspect. 2006;114(7):1133–8.

    Article  PubMed  CAS  Google Scholar 

  51. Main KM, Kiviranta H, Virtanen HE, Sundqvist E, Tuomisto JT, Tuomisto J, et al. Flame retardants in placenta and breast milk and cryptorchidism in newborn boys. Environ Health Perspect. 2007;115(10):1519–26.

    PubMed  CAS  Google Scholar 

  52. Shen H, Main KM, Andersson AM, Damgaard IN, Virtanen HE, Skakkebaek NE, et al. Concentrations of persistent organochlorine compounds in human milk and placenta are higher in Denmark than in Finland. Hum Reprod. 2008;23(1):201–10.

    Article  PubMed  CAS  Google Scholar 

  53. Brucker-Davis F, Wagner-Mahler K, Delattre I, Ducot B, Ferrari P, Bongain A, 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  PubMed  CAS  Google Scholar 

  54. Palmer JR, Herbst AL, Noller KL, Boggs DA, Troisi R, Titus-Ernstoff L, et al. Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study. Environ Health. 2009;8:37.

    Article  PubMed  Google Scholar 

  55. Palmer JR, Wise LA, Robboy SJ, Titus-Ernstoff L, Noller KL, Herbst AL, et al. Hypospadias in sons of women exposed to diethylstilbestrol in utero. Epidemiology. 2005;16(4):583–6.

    Article  PubMed  Google Scholar 

  56. Christiansen S, Scholze M, Dalgaard M, Vinggaard AM, Axelstad M, Kortenkamp A, et al. Synergistic disruption of external male sex organ development by a mixture of four antiandrogens. Environ Health Perspect. 2009;117(12):1839–46.

    PubMed  CAS  Google Scholar 

Additional References

  • European science foundation. Male reproductive health. http://www.esf.org/publications/science-policy-briefings.html

  • Fernández MF, Rivas A, Olea-Serrano F, Cerrillo I, Molina-Molina JM, Araque P, et al. Assessment of total effective xenoestrogen burden in adipose tissue and identification of chemicals responsible for the combined estrogenic effect. Anal Bioanal Chem. 2004;379(1):163–70.

    Article  PubMed  Google Scholar 

  • Main KM, Skakkebaek NE, Virtanen HE, Toppari J. Genital anomalies in boys and the environment. Best Pract Res Clin Endocrinol Metab. 2010;24(2):279–89. Review.

    Article  PubMed  Google Scholar 

  • Paulozzi LJ, Erickson JD, Jackson RJ. Hypospadias trends in two American surveillance systems. Pediatrics. 1997;100:831–4.

    Article  PubMed  CAS  Google Scholar 

  • Robaire B, Hales BF. Mechanism of action of cyclophosphamide as a malemediated developmental toxicant. Adv Exp Med Biol. 2003;518:169–80.

    Article  PubMed  CAS  Google Scholar 

  • Weidner IS, Møller H, Jensen TK, Skakkebæk NE. Risk factors for cryptorchidism and hypospadias. J Urol. 1999;161(5):1606–9.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We are indebted to Richard Davies for editorial assistance. This study was supported by grants from the Junta de Andalucía (grant numbers P09-CTS-5488 and SAS 07/0133), Spanish Ministry of Science and Innovation (Ramón y Cajal Programme to MF. Fernandez), Spanish Ministry of Health (CIBERESP), and the European Union Commission (Environ. Reprod. Health, QLK4-1999-01422; EDEN, QLRT-2001-00603; CASCADE, Food-CT-2003-506319; and CONTAMED, 2009-212502, projects).

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Correspondence to Mariana F. Fernandez .

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Fernandez, M.F., Olea, N. (2012). Developmental Exposure to Endocrine Disruptors and Male Urogenital Tract Malformations. In: Diamanti-Kandarakis, E., Gore, A. (eds) Endocrine Disruptors and Puberty. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-60761-561-3_8

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