Current Urology Reports

, Volume 13, Issue 4, pp 307–310 | Cite as

An Update on Phthalates and Male Reproductive Development and Function

Pediatric Urology (R Grady, Section editor)

Abstract

Phthalates are part of a class of high-volume industrial chemicals used ubiquitously in health care as well as household products. Biomarker studies have confirmed the widespread presence of these chemicals in both humans and animals. As a class, phthalates have been implicated in diseases and birth anomalies of the genitourinary tract including hypospadias, testis anomalies, and subfertility. This article will discuss the current data surrounding these chemicals and their association with genital anomalies including genital anomalies and infertility.

Keywords

Phthalates Anogenital distance Infertility Hypospadias Cryptorchism Endocrine disruptor Birth anomalies Genitourinary tract Testis anomalies Subfertility 

Notes

Disclosures

No potential conflicts of interest relevant to this article were reported.

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    CDC, Third national report on human exposure to environmental chemicals: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences: Atlanta, GA; 2005.Google Scholar
  2. 2.
    Hauser R, et al. Medications as a source of human exposure to phthalates. Environ Health Perspect. 2004;112(6):751–3.PubMedCrossRefGoogle Scholar
  3. 3.
    Rudel RA, et al. Phthalates, alkylphenols, pesticides, polybrominated diphenyl ethers, and other endocrine-disrupting compounds in indoor air and dust. Environ Sci Technol. 2003;37(20):4543–53.PubMedCrossRefGoogle Scholar
  4. 4.
    Rudel RA, et al. Phthalates, alkylphenols, pesticides, polybrominated diphenyl ethers, and other endocrine-disrupting compounds in indoor air and dust. Environ Sci Technol. 2003;37(20):4543–53.PubMedCrossRefGoogle Scholar
  5. 5.
    Wormuth M, et al. What are the sources of exposure to eight frequently used phthalic acid esters in Europeans? Risk Anal. 2006;26(3):803–24.PubMedCrossRefGoogle Scholar
  6. 6.
    Swan SH. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environ Res. 2008;108(2):177–84.PubMedCrossRefGoogle Scholar
  7. 7.
    Main KM, et al. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environ Heal Perspect. 2006;114(2):270–6.CrossRefGoogle Scholar
  8. 8.
    Huang PC, et al. Association between prenatal exposure to phthalates and the health of newborns. Environ Int. 2008.Google Scholar
  9. 9.
    Akingbemi BT, et al. Phthalate-induced Leydig cell hyperplasia is associated with multiple endocrine disturbances. PNAS. 2004;101(3):775–80.PubMedCrossRefGoogle Scholar
  10. 10.
    Borch J, et al. Steroidogenesis in fetal male rats is reduced by DEHP and DINP, but endocrine effects of DEHP are not modulated by DEHA in fetal, prepubertal and adult male rats. Reprod Toxicol. 2004;18:53–61.PubMedCrossRefGoogle Scholar
  11. 11.
    Foster PM, Cattley RC, Mylchreest E. Effects of di-n-butyl phthalate (DBP) on male reproductive development in the rat: implications for human risk assessment. Food Chem Toxicol. 2000;38 Suppl 1:S97–9 [Review] [16 refs].PubMedGoogle Scholar
  12. 12.
    Mylchreest E, Foster PM. DBP exerts its antiandrogenic activity by indirectly interfering with androgen signaling pathways. Toxicol Appl Pharmacol. 2000;168(2):174–5.CrossRefGoogle Scholar
  13. 13.
    Wohlfahrt-Veje C, Main KM, Skakkebaek NE. Testicular dysgenesis syndrome: foetal origin of adult reproductive problems. Clin Endocrinol (Oxf). 2009;71(4):459–65.CrossRefGoogle Scholar
  14. 14.
    Wilson VS, et al. Diverse mechanisms of anti-androgen action: impact on male rat reproductive tract development. Int J Androl. 2008;31(2):178–87.PubMedCrossRefGoogle Scholar
  15. 15.
    Swan SH, Elkin EP, Fenster L. The question of declining sperm density revisited: an analysis of 101 studies published 1934–1996. Environ Health Perspect. 2000;108(10):961–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Duty SM, et al. Phthalate exposure and human semen parameters. Epidemiology. 2003;14(3):269–77.PubMedGoogle Scholar
  17. 17.
    Latini G, et al. Phthalate exposure and male infertility. Toxicology. 2006;226(2–3):90–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Lamb JCT, et al. Reproductive effects of four phthalic acid esters in the mouse. Toxicol Appl Pharmacol. 1987;88(2):255–69.PubMedCrossRefGoogle Scholar
  19. 19.
    Gray Jr LE, et al. Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol Sci. 2000;58:350–65.PubMedCrossRefGoogle Scholar
  20. 20.
    Lee BM, Koo HJ. Hershberger assay for antiandrogenic effects of phthalates. J Toxicol Environ Heal. 2007;70:1365–70.CrossRefGoogle Scholar
  21. 21.
    Foster PM. Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. Int J Androl. 2006;29(1):140–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Gray LE, et al. Use of the laboratory rat as a model in endocrine disruptor screening and testing. ILAR J Nat Res Council Instit Lab Anima Resou. 2004;45(4):425–37.Google Scholar
  23. 23.
    Hotchkiss AK, et al. Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague–Dawley rat. Environ Health Perspect. 2002;110 Suppl 3:435–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Pant N, et al. Environmental and experimental exposure of phthalate esters: the toxicological consequence on human sperm. Hum Exp Toxicol. 2011;30(6):507–14.PubMedCrossRefGoogle Scholar
  25. 25.
    Hsieh MH, et al. Associations among hypospadias, cryptorchidism, anogenital distance, and endocrine disruption. Curr Urol Rep. 2008;9(2):137–42.PubMedCrossRefGoogle Scholar
  26. 26.
    Swan SH, et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Heal Perspect. 2005;113(8):1056–61.CrossRefGoogle Scholar
  27. 27.
    Howdeshell KL, et al. A mixture of five phthalate esters inhibits fetal testicular testosterone production in the Sprague Dawley rat in a cumulative, dose additive manner. Toxicol Sci. 2008.Google Scholar
  28. 28.
    Huang PC, et al. Association between prenatal exposure to phthalates and the health of newborns. Environ Int. 2009;35(1):14–20.PubMedCrossRefGoogle Scholar
  29. 29.
    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.PubMedCrossRefGoogle Scholar
  30. 30.
    Tranfo G, et al. Urinary phthalate monoesters concentration in couples with infertility problems. Toxicol Lett. 2011.Google Scholar
  31. 31.
    Arbuckle TE, et al. Meeting report: measuring endocrine-sensitive endpoints within the first years of life. Environ Health Perspect. 2008;116(7):948–51.PubMedCrossRefGoogle Scholar
  32. 32.
    •• Mendiola J, et al. Shorter anogenital distance predicts poorer semen quality in young men in Rochester, New York. Environ Health Perspect. 2011;119(7):958–63. This study supports the testicular dysgenesis hypothesis in humans, which links abnormalities during in utero gonad development with future reproductive health abnormalities. PubMedCrossRefGoogle Scholar
  33. 33.
    •• Eisenberg ML, et al. The relationship between anogenital distance and the efficacy of varicocele repair. BJU Int. 2012. This study supports the testicular dysgenesis hypothesis in humans, which links abnormalities during in utero gonad development with future reproductive health abnormalities. Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.The University of Washington School of MedicineSeattleUSA
  2. 2.Seattle Children’s HospitalSeattleUSA
  3. 3.The University of Washington School of Public HealthSeattleUSA

Personalised recommendations