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Journal of Endocrinological Investigation

, Volume 41, Issue 6, pp 639–645 | Cite as

Impact of perfluorochemicals on human health and reproduction: a male’s perspective

  • C. ForestaEmail author
  • S. Tescari
  • A. Di Nisio
Short Review

Abstract

Perfluoroalkyl compounds (PFCs) are a class of organic molecules used in industry and consumer products. PFCs are non-biodegradable and bioaccumulate in the environment and for these reasons they have been a major subject of research regarding their toxicity, environmental fate, and sources of human exposure, since they have been shown to induce severe health consequences, such as neonatal mortality, neurotoxicity and immunotoxicity. The aim of this review is to explore the existing knowledge of the interplay between PFCs exposure and human health, with a focus on male reproductive health, given the emerging gender differences in PFCs clearance and their interaction with sex hormones receptors. A comprehensive PUBMED search was performed using relevant key terms for PFCs and male fertility. Different degrees of evidence suggest an impairment of semen parameters and sex hormones in relation to PFCs exposure. These preliminary results point towards a sex-dependent pharmacodynamics and clearance, with males having a much higher tendency to accumulation. Moreover, because of the widespread environmental occurrence of these chemicals, along with their ability to cross the placental barrier, exposure of the foetus to these compounds is inevitable. This is of concern because foetal development of the male reproductive organs may be disturbed by exposure to exogenous factors. These findings clearly suggest an antiandrogenic potential of PFCs and a link between endocrine disruptors and disorders of male health.

Keywords

Endocrine disruptors Infertility Androgen receptor Sexual development Male health 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

Ethical approval

This article does not contain studies with human participants or animals performed by any of the authors.

Informed consent

No informed consent.

Supplementary material

40618_2017_790_MOESM1_ESM.tif (87 kb)
Supplementary material 1 (TIFF 87 kb)

References

  1. 1.
    Conder JM, Hoke RA, De Wolf W et al (2008) Are PFCAs bioaccumulative? A critical review and comparison with regulatory criteria and persistent lipophilic compounds. Environ Sci Technol 42:995–1003CrossRefPubMedGoogle Scholar
  2. 2.
    Steenland K, Fletcher T, Savitz DA (2010) Epidemiologic evidence on the health effects of perfluorooctanoic acid (PFOA). Environ Health Perspect 118:1100–1108.  https://doi.org/10.1289/ehp.0901827 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Giesy JP, Kannan K (2002) Perfluorochemical surfactants in the environment. Environ Sci Technol 36:146A–152ACrossRefPubMedGoogle Scholar
  4. 4.
    Han X, Snow TA, Kemper RA, Jepson GW (2003) Binding of perfluorooctanoic acid to rat and human plasma proteins. Chem Res Toxicol 16:775–781.  https://doi.org/10.1021/tx034005w CrossRefPubMedGoogle Scholar
  5. 5.
    Fromme H, Tittlemier SA, Völkel W et al (2009) Perfluorinated compounds—exposure assessment for the general population in western countries. Int J Hyg Environ Health 212:239–270.  https://doi.org/10.1016/j.ijheh.2008.04.007 CrossRefPubMedGoogle Scholar
  6. 6.
    Olsen GW, Lange CC, Ellefson ME et al (2012) Temporal trends of perfluoroalkyl concentrations in American Red Cross Adult Blood Donors, 2000–2010. Environ Sci Technol 46:6330–6338.  https://doi.org/10.1021/es300604p CrossRefPubMedGoogle Scholar
  7. 7.
    Raymer JH, Michael LC, Studabaker WB et al (2012) Concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and their associations with human semen quality measurements. Reprod Toxicol 33:419–427.  https://doi.org/10.1016/j.reprotox.2011.05.024 CrossRefPubMedGoogle Scholar
  8. 8.
    Kubwabo C, Kosarac I, Lalonde K (2013) Determination of selected perfluorinated compounds and polyfluoroalkyl phosphate surfactants in human milk. Chemosphere 91:771–777.  https://doi.org/10.1016/j.chemosphere.2013.02.011 CrossRefPubMedGoogle Scholar
  9. 9.
    Kim S, Choi K, Ji K et al (2011) Trans-placental transfer of thirteen perfluorinated compounds and relations with fetal thyroid hormones. Environ Sci Technol 45:7465–7472.  https://doi.org/10.1021/es202408a CrossRefPubMedGoogle Scholar
  10. 10.
    Maestri L, Negri S, Ferrari M et al (2006) Determination of perfluorooctanoic acid and perfluorooctanesulfonate in human tissues by liquid chromatography/single quadrupole mass spectrometry. Rapid Commun Mass Spectrom 20:2728–2734.  https://doi.org/10.1002/rcm.2661 CrossRefPubMedGoogle Scholar
  11. 11.
    Haug LS, Huber S, Becher G, Thomsen C (2011) Characterisation of human exposure pathways to perfluorinated compounds—comparing exposure estimates with biomarkers of exposure. Environ Int 37:687–693.  https://doi.org/10.1016/j.envint.2011.01.011 CrossRefPubMedGoogle Scholar
  12. 12.
    Apelberg BJ, Goldman LR, Calafat AM et al (2007) Determinants of fetal exposure to polyfluoroalkyl compounds in Baltimore, Maryland. Environ Sci Technol 41:3891–3897CrossRefPubMedGoogle Scholar
  13. 13.
    Needham LL, Grandjean P, Heinzow B et al (2011) Partition of environmental chemicals between maternal and fetal blood and tissues. Environ Sci Technol 45:1121–1126.  https://doi.org/10.1021/es1019614 CrossRefPubMedGoogle Scholar
  14. 14.
    Skakkebaek NE, Rajpert-De Meyts E, Main KM (2001) Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod 16:972–978CrossRefPubMedGoogle Scholar
  15. 15.
    Lau C (2012) Perfluorinated compounds. In: EXS. pp 47–86Google Scholar
  16. 16.
    Biegel LB, Liu RCM, Hurtt ME, Cook JC (1995) Effects of ammonium perfluorooctanoate on leydig-cell function. In Vitro, in Vivo, and ex Vivo Studies. Toxicol Appl Pharmacol 134:18–25.  https://doi.org/10.1006/taap.1995.1164 CrossRefPubMedGoogle Scholar
  17. 17.
    Shi Z, Zhang H, Liu Y et al (2007) Alterations in gene expression and testosterone synthesis in the testes of male rats exposed to perfluorododecanoic acid. Toxicol Sci 98:206–215.  https://doi.org/10.1093/toxsci/kfm070 CrossRefPubMedGoogle Scholar
  18. 18.
    Wan HT, Zhao YG, Wong MH et al (2011) Testicular signaling is the potential target of perfluorooctanesulfonate-mediated subfertility in male Mice. Biol Reprod 84:1016–1023.  https://doi.org/10.1095/biolreprod.110.089219 CrossRefPubMedGoogle Scholar
  19. 19.
    Zhang H, Lu Y, Luo B et al (2014) Proteomic analysis of mouse testis reveals perfluorooctanoic acid-induced reproductive dysfunction via direct disturbance of testicular steroidogenic machinery. J Proteome Res 13:3370–3385.  https://doi.org/10.1021/pr500228d CrossRefPubMedGoogle Scholar
  20. 20.
    Kang JS, Choi JS, Park JW (2016) Transcriptional changes in steroidogenesis by perfluoroalkyl acids (PFOA and PFOS) regulate the synthesis of sex hormones in H295R cells. Chemosphere 155:436–443.  https://doi.org/10.1016/j.chemosphere.2016.04.070 CrossRefPubMedGoogle Scholar
  21. 21.
    Joensen UN, Bossi R, Leffers H et al (2009) Do Perfluoroalkyl compounds impair human semen quality? Environ Health Perspect 117:923–927.  https://doi.org/10.1289/ehp.0800517 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Joensen UN, Veyrand B, Antignac JP et al (2013) PFOS (perfluorooctanesulfonate) in serum is negatively associated with testosterone levels, but not with semen quality, in healthy men. Hum Reprod 28:599–608.  https://doi.org/10.1093/humrep/des425 CrossRefPubMedGoogle Scholar
  23. 23.
    Specht IO, Hougaard KS, Spanò M et al (2012) Sperm DNA integrity in relation to exposure to environmental perfluoroalkyl substances—a study of spouses of pregnant women in three geographical regions. Reprod Toxicol 33:577–583.  https://doi.org/10.1016/j.reprotox.2012.02.008 CrossRefPubMedGoogle Scholar
  24. 24.
    Louis GMB, Chen Z, Schisterman EF et al (2015) Perfluorochemicals and human semen quality: the LIFE study. Environ Health Perspect 123:57–63.  https://doi.org/10.1289/ehp.1307621 PubMedCrossRefGoogle Scholar
  25. 25.
    Toft G, Jönsson BAG, Lindh CH et al (2012) Exposure to perfluorinated compounds and human semen quality in arctic and European populations. Hum Reprod 27:2532–2540.  https://doi.org/10.1093/humrep/des185 CrossRefPubMedGoogle Scholar
  26. 26.
    Governini L, Guerranti C, De Leo V et al (2015) Chromosomal aneuploidies and DNA fragmentation of human spermatozoa from patients exposed to perfluorinated compounds. Andrologia 47:1012–1019.  https://doi.org/10.1111/and.12371 CrossRefPubMedGoogle Scholar
  27. 27.
    López-Doval S, Salgado R, Pereiro N et al (2014) Perfluorooctane sulfonate effects on the reproductive axis in adult male rats. Environ Res 134:158–168.  https://doi.org/10.1016/j.envres.2014.07.006 CrossRefPubMedGoogle Scholar
  28. 28.
    López-Doval S, Salgado R, Fernández-Pérez B, Lafuente A (2015) Possible role of serotonin and neuropeptide Y on the disruption of the reproductive axis activity by perfluorooctane sulfonate. Toxicol Lett 233:138–147.  https://doi.org/10.1016/j.toxlet.2015.01.012 CrossRefPubMedGoogle Scholar
  29. 29.
    Pereiro N, Moyano R, Blanco A, Lafuente A (2014) Regulation of corticosterone secretion is modified by PFOS exposure at different levels of the hypothalamic–pituitary–adrenal axis in adult male rats. Toxicol Lett 230:252–262.  https://doi.org/10.1016/j.toxlet.2014.01.003 CrossRefPubMedGoogle Scholar
  30. 30.
    Qiu L, Zhang X, Zhang X et al (2013) Sertoli cell is a potential target for perfluorooctane sulfonate-induced reproductive dysfunction in male mice. Toxicol Sci 135:229–240.  https://doi.org/10.1093/toxsci/kft129 CrossRefPubMedGoogle Scholar
  31. 31.
    Jensen AA, Leffers H (2008) Emerging endocrine disrupters: perfluoroalkylated substances. Int J Androl 31:161–169.  https://doi.org/10.1111/j.1365-2605.2008.00870.x CrossRefPubMedGoogle Scholar
  32. 32.
    Zhang Y, Beesoon S, Zhu L, Martin JW (2013) Biomonitoring of perfluoroalkyl acids in human urine and estimates of biological half-life. Environ Sci Technol 47:10619–10627.  https://doi.org/10.1021/es401905e CrossRefPubMedGoogle Scholar
  33. 33.
    López-Doval S, Salgado R, Lafuente A (2016) The expression of several reproductive hormone receptors can be modified by perfluorooctane sulfonate (PFOS) in adult male rats. Chemosphere 155:488–497.  https://doi.org/10.1016/j.chemosphere.2016.04.081 CrossRefPubMedGoogle Scholar
  34. 34.
    Vested A, Ramlau-Hansen CH, Olsen SF et al (2013) Associations of in Utero exposure to perfluorinated alkyl acids with human semen quality and reproductive hormones in adult men. Environ Health Perspect 121:453–458.  https://doi.org/10.1289/ehp.1205118 PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    La Rocca C, Alessi E, Bergamasco B et al (2012) Exposure and effective dose biomarkers for perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in infertile subjects: preliminary results of the PREVIENI project. Int J Hyg Environ Health 215:206–211.  https://doi.org/10.1016/j.ijheh.2011.10.016 CrossRefPubMedGoogle Scholar
  36. 36.
    La Rocca C, Tait S, Guerranti C et al (2015) Exposure to endocrine disruptors and nuclear receptors gene expression in infertile and fertile men from Italian areas with different environmental features. Int J Environ Res Public Health 12:12426–12445.  https://doi.org/10.3390/ijerph121012426 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Dehm SM, Tindall DJ (2007) Androgen receptor structural and functional elements: role and regulation in prostate cancer. Mol Endocrinol 21:2855–2863.  https://doi.org/10.1210/me.2007-0223 CrossRefPubMedGoogle Scholar
  38. 38.
    Gao W, Bohl CE, Dalton JT (2005) Chemistry and structural biology of androgen receptor. Chem Rev 105:3352–3370.  https://doi.org/10.1021/cr020456u CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Kjeldsen LS, Bonefeld-Jørgensen EC (2013) Perfluorinated compounds affect the function of sex hormone receptors. Environ Sci Pollut Res 20:8031–8044.  https://doi.org/10.1007/s11356-013-1753-3 CrossRefGoogle Scholar
  40. 40.
    Luccio-Camelo DC, Prins GS (2011) Disruption of androgen receptor signaling in males by environmental chemicals. J Steroid Biochem Mol Biol 127:74–82.  https://doi.org/10.1016/j.jsbmb.2011.04.004 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Paoli D, Giannandrea F, Gallo M et al (2015) Exposure to polychlorinated biphenyls and hexachlorobenzene, semen quality and testicular cancer risk. J Endocrinol Invest 38:745–752.  https://doi.org/10.1007/s40618-015-0251-5 CrossRefPubMedGoogle Scholar
  42. 42.
    Austin ME, Kasturi BS, Barber M et al (2003) Neuroendocrine effects of perfluorooctane sulfonate in rats. Environ Health Perspect 111:1485–1489CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Li N, Mruk DD, Chen H et al (2016) Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43. Sci Rep 6:29667.  https://doi.org/10.1038/srep29667 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Kim SJ, Heo SH, Lee DS et al (2016) Gender differences in pharmacokinetics and tissue distribution of 3 perfluoroalkyl and polyfluoroalkyl substances in rats. Food Chem Toxicol 97:243–255.  https://doi.org/10.1016/j.fct.2016.09.017 CrossRefPubMedGoogle Scholar
  45. 45.
    Chang S-C, Noker PE, Gorman GS et al (2012) Comparative pharmacokinetics of perfluorooctanesulfonate (PFOS) in rats, mice, and monkeys. Reprod Toxicol 33:428–440.  https://doi.org/10.1016/j.reprotox.2011.07.002 CrossRefPubMedGoogle Scholar
  46. 46.
    Hundley SG, Sarrif AM, Kennedy GL (2006) Absorption, distribution, and excretion of ammonium perfluorooctanoate (APFO) after oral administration to various species. Drug Chem Toxicol 29:137–145.  https://doi.org/10.1080/01480540600561361 CrossRefPubMedGoogle Scholar
  47. 47.
    Hanhijärvi H, Ylinen M, Haaranen T, Nevalainen T (1988) A proposed species difference in the renal excretion of perfluoro octanoic acid in the Beagle dog and rat. In: New developments in biosciences: their implications for laboratory animal science. Springer Netherlands, Dordrecht, pp 409–412Google Scholar
  48. 48.
    Weaver YM, Ehresman DJ, Butenhoff JL, Hagenbuch B (2010) Roles of rat renal organic anion transporters in transporting perfluorinated carboxylates with different chain lengths. Toxicol Sci 113:305–314.  https://doi.org/10.1093/toxsci/kfp275 CrossRefPubMedGoogle Scholar
  49. 49.
    Butenhoff JL, Kennedy GL, Hinderliter PM et al (2004) Pharmacokinetics of perfluorooctanoate in cynomolgus monkeys. Toxicol Sci 82:394–406.  https://doi.org/10.1093/toxsci/kfh302 CrossRefPubMedGoogle Scholar
  50. 50.
    Lau C, Anitole K, Hodes C et al (2007) Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicol Sci 99:366–394.  https://doi.org/10.1093/toxsci/kfm128 CrossRefPubMedGoogle Scholar
  51. 51.
    Nakayama S, Harada K, Inoue K et al (2005) Distributions of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in Japan and their toxicities. Environ Sci 12:293–313PubMedGoogle Scholar
  52. 52.
    Kudo N, Kawashima Y (2003) Toxicity and toxicokinetics of perfluorooctanoic acid in humans and animals. J Toxicol Sci 28:49–57CrossRefPubMedGoogle Scholar
  53. 53.
    Kennedy GL, Butenhoff JL, Olsen GW et al (2004) The toxicology of perfluorooctanoate. Crit Rev Toxicol 34:351–384CrossRefPubMedGoogle Scholar
  54. 54.
    Olsen GW, Burris JM, Ehresman DJ et al (2007) Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ Health Perspect 115:1298–1305.  https://doi.org/10.1289/ehp.10009 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Brede E, Wilhelm M, Göen T et al (2010) Two-year follow-up biomonitoring pilot study of residents’ and controls’ PFC plasma levels after PFOA reduction in public water system in Arnsberg, Germany. Int J Hyg Environ Health 213:217–223.  https://doi.org/10.1016/j.ijheh.2010.03.007 CrossRefPubMedGoogle Scholar
  56. 56.
    Bartell SM, Calafat AM, Lyu C et al (2010) Rate of decline in serum PFOA concentrations after granular activated carbon filtration at two public water systems in Ohio and West Virginia. Environ Health Perspect 118:222–228.  https://doi.org/10.1289/ehp.0901252 CrossRefPubMedGoogle Scholar
  57. 57.
    Tan Y-M, Clewell HJ, Andersen ME (2008) Time dependencies in perfluorooctylacids disposition in rat and monkeys: a kinetic analysis. Toxicol Lett 177:38–47.  https://doi.org/10.1016/j.toxlet.2007.12.007 CrossRefPubMedGoogle Scholar
  58. 58.
    Cui L, Liao C, Zhou Q et al (2010) Excretion of PFOA and PFOS in male rats during a subchronic exposure. Arch Environ Contam Toxicol 58:205–213.  https://doi.org/10.1007/s00244-009-9336-5 CrossRefPubMedGoogle Scholar
  59. 59.
    Han X, Nabb DL, Russell MH et al (2012) Renal elimination of perfluorocarboxylates (PFCAs). Chem Res Toxicol 25:35–46.  https://doi.org/10.1021/tx200363w CrossRefPubMedGoogle Scholar
  60. 60.
    Fu J, Gao Y, Cui L et al (2016) Occurrence, temporal trends, and half-lives of perfluoroalkyl acids (PFAAs) in occupational workers in China. Sci Rep 6:38039.  https://doi.org/10.1038/srep38039 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Harada K, Inoue K, Morikawa A et al (2005) Renal clearance of perfluorooctane sulfonate and perfluorooctanoate in humans and their species-specific excretion. Environ Res 99:253–261.  https://doi.org/10.1016/j.envres.2004.12.003 CrossRefPubMedGoogle Scholar
  62. 62.
    Nakagawa H, Terada T, Harada KH et al (2009) Human organic anion transporter hOAT4 is a transporter of perfluorooctanoic acid. Basic Clin Pharmacol Toxicol 105:136–138.  https://doi.org/10.1111/j.1742-7843.2009.00409.x CrossRefPubMedGoogle Scholar
  63. 63.
    Kudo N, Katakura M, Sato Y, Kawashima Y (2002) Sex hormone-regulated renal transport of perfluorooctanoic acid. Chem Biol Interact 139:301–316.  https://doi.org/10.1016/S0009-2797(02)00006-6 CrossRefPubMedGoogle Scholar
  64. 64.
    Fei C, McLaughlin JK, Tarone RE, Olsen J (2007) Perfluorinated chemicals and fetal growth: a study within the Danish National Birth Cohort. Environ Health Perspect 115:1677–1682.  https://doi.org/10.1289/ehp.10506 CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Inoue K, Okada F, Ito R et al (2004) Perfluorooctane sulfonate (PFOS) and related perfluorinated compounds in human maternal and cord blood samples: assessment of PFOS exposure in a susceptible population during pregnancy. Environ Health Perspect 112:1204–1207CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Post GB, Cohn PD, Cooper KR (2012) Perfluorooctanoic acid (PFOA), an emerging drinking water contaminant: a critical review of recent literature. Environ Res 116:93–117.  https://doi.org/10.1016/j.envres.2012.03.007 CrossRefPubMedGoogle Scholar
  67. 67.
    Cho E, Montgomery RB, Mostaghel EA (2014) Minireview: SLCO and ABC transporters: a role for steroid transport in prostate cancer progression. Endocrinology 155:4124–4132.  https://doi.org/10.1210/en.2014-1337 CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Barry V, Winquist A, Steenland K (2013) Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environ Health Perspect 121:1313–1318.  https://doi.org/10.1289/ehp.1306615 PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Vieira VM, Hoffman K, Shin HM et al (2013) Perfluorooctanoic acid exposure and cancer outcomes in a contaminated community: a geographic analysis. Environ Health Perspect 121:318–323.  https://doi.org/10.1289/ehp.1205829 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Eriksen KT, Sorensen M, McLaughlin JK et al (2009) Perfluorooctanoate and perfluorooctanesulfonate plasma levels and risk of cancer in the general danish population. J Natl Cancer Inst 101:605–609.  https://doi.org/10.1093/jnci/djp041 CrossRefPubMedGoogle Scholar
  71. 71.
    Buhrke T, Kibellus A, Lampen A (2013) In vitro toxicological characterization of perfluorinated carboxylic acids with different carbon chain lengths. Toxicol Lett 218:97–104.  https://doi.org/10.1016/j.toxlet.2013.01.025 CrossRefPubMedGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2017

Authors and Affiliations

  1. 1.Department of Medicine, Unit of Andrology and Medicine of Human ReproductionUniversità degli Studi di PadovaPaduaItaly

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