Endocrine disruptors (EDs) are chemical substances that affect physiological processes in the organism via hormonal regulation. The EDs are present in the environment and objects of everyday use. They are often detected in food, particularly released from packaging of canned food, but also from plastic water bottles, and they are also found in cosmetics and fertilizers. They are commonly detected in children's toys, banknotes, receipts and many more objects. Permanent and long-term utilization of EDs has harmful effects on human reproductive health mainly by interference with sex hormone synthesis and mechanism of action. The endocrine disruptors show many negative effects on male reproductive system. Any change during synthesis or activity of sex hormones can cause abnormal reproduction, including developmental anomalies of the sexual system, disruption of testicular development or deterioration of sperm quality. Mainly the impact on the development of testicles in prenatal and early postnatal period can be crucial for reproductive health in males. This review provides an overview of the EDs and their possible impact on reproductive health in males with focus on sperm quality and development of testicles.
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1. Welsh M Saunders P Fisken M Scott H Hutchison G Smith L Sharpe LM. Identification in rats of a programming window for reproductive tract masculinization disruption of which leads to hypospadias and cryptorchidism. Journal of Clinical Investigation. 2008;118(4):1479-90; DOI:10.1172/JCI34241.
2. Chiba K Kondo Y Yamaguchi K Miyake H Fujisawa M. Inhibition of Claudin-11 and Occludin Expression in Rat Sertoli Cells by Mono-(2-Ethylhexyl) Phthalate Through p44/42 Mitogen-Activated Protein Kinase Pathway. Journal of Andrology. 2012;33(3):368-74; DOI:10.2164/jandrol.111.013664.
3. Kitamura S Suzuki T Sanoh S Kohta R Jinno N Sugihara K Yoshihara S Fujimoto N Watanabe H Ohta S. Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related compounds. Toxicological Sciences. 2005;84(2):249-59; DOI:10.1093/toxsci/kfi074.
4. Wetherill Y Akingbemi B Kanno J McLachlan J Nadal A Sonnenscheing C Watson CS Zoeller RT Belcher SM. In vitro molecular mechanisms of bisphenol A action. Reproductive Toxicology. 2007;24(2):178-98; DOI:10.1016/j.reprotox.2007.05.010.
5. Skakkebaek N Rajpert-De Meyts E Louis G Toppari J Andersson A Eisenberg M Jensen TK Jorgensen N Swan SH Sapra KJ Ziebe S Priskorn L Juul A. Male reproductive disorders and fertility trends: influences of environment and genetic susceptibility. Physiological Reviews. 2016;96(1):55-97; DOI:10.1152/physrev.00017.2015.
6. Vitku J Sosvorova L Chlupacova T Hampl R Hill M Sobotka V Heracek J Bicikova M Starka L. Differences in Bisphenol A and Estrogen Levels in the Plasma and Seminal Plasma of Men With Different Degrees of Infertility. Physiological Research. 2015;64:S303-S11.
7. Hallmark N Walker M McKinnell C Mahood I Scott H Bayne R Coutts S Anderson RA Greig I Morris K Sharpe RM. Effects of monobutyl and di(n-butyl) phthalate in vitro on steroidogenesis and Leydig cell aggregation in fetal testis explants from the rat: Comparison with effects in vivo in the fetal rat and neonatal marmoset and in vitro in the human. Environmental Health Perspectives. 2007;115(3):390-6; DOI:10.1289/ehp.9490.
8. Lovekamp-Swan T Jetten A Davis B. Dual activation of PPAR alpha and PPAR gamma by mono-(2-ethylhexyl) phthalate in rat ovarian granulosa cells. Molecular and Cellular Endocrinology. 2003;201(1-2):133-41.
9. Akingbemi B Ge R Klinefelter G Zirkin B Hardy M. Phthalate-induced Leydig cell hyperplasia is associated with multiple endocrine disturbances. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(3):775-80; DOI:10.1073/pnas.0305977101.
10. Zhao Y Ao H Chen L Sottas C Ge R Li L Zhang YH. Mono-(2-ethylhexyl) phthalate affects the steroidogenesis in rat Leydig cells through provoking ROS perturbation. Toxicology in Vitro. 2012;26(6):950-5; DOI:10.1016/j.tiv.2012.04.003.
11. Li L Jester W Laslett A Orth J. A single dose of di-(2-ethylhexyl) phthalate in neonatal rats alters gonocytes reduces Sertoli cell proliferation and decreases cyclin D2 expression. Toxicology and Applied Pharmacology. 2000;166(3):222-9; DOI:10.1006/taap.2000.8972.
12. Toppari J Larsen J Christiansen P Giwercman A Grandjean P Guillette L Jegou B Jensen TK Jouannet P Keiding N Leffers H McLachlan JA Meyer O Muller J RajpertDeMeyts E Scheike T Sharpe R Sumpter J Skakkebaek NE Male reproductive health and environmental xenoestrogens. Environmental Health Perspectives. 1996;104:741-803.
13. McLachlan J Newbold R Bullock B. Reproductive-tract lesions in male mice exposed prenatally to diethylstilbestrol. Science. 1975;190(4218):991-2.
14. Strohsnitter WC Noller KL Hoover RN Robboy SJ Palmer JR Titus-Ernstoff L Kaufman RH Adam E Herbst AL Hatch EE. Cancer risk in men exposed in utero to diethylstilbestrol. J Natl Cancer Inst. 2001;93(7):545–51.
15. Giannandrea F Paoli D Figa-Talamanca I Lombardo F Lenzi A Gandini L. Effect of endogenous and exogenous hormones on testicular cancer: the epidemiological evidence. International Journal of Developmental Biology. 2013;57(2-4):255-63; DOI:10.1387/ijdb.130015fg.
16. Zalmanova T Hoskova K Nevoral J Prokesova S Zamostna K Kott T Petr J. Bisphenol S instead of bisphenol A: a story of reproductive disruption by regretable substitution - a review. Czech Journal of Animal Science. 2016;61(10):433-49.
17. Vilela J Hartmann A Silva E Cardoso T Corcini C Varela A Martinez PE Colares EP. Sperm impairments in adult vesper mice (Calomys laucha) caused by in utero exposure to bisphenol A. Andrologia. 2014;46(9):971-8; DOI:10.1111/and.12182.
18. Doyle T Bowman J Windell V McLean D Kim K. Transgenerational Effects of Di-(2-ethylhexyl) Phthalate on Testicular Germ Cell Associations and Spermatogonial Stem Cells in Mice. Biology of Reproduction. 2013;88(5); DOI:10.1095/biolreprod.112.106104.
19. Marcoccia D Pellegrini M Fiocchetti M Lorenzetti S Marino M. Food components and contaminants as (anti)androgenic molecules. Genes and Nutrition. 2017;12; DOI:10.1186/s12263-017-0555-5.
20. Mylchreest E Wallace D Cattley R Foster P. Dose-dependent alterations in androgen-regulated male reproductive development in rats exposed to di(n-butyl) phthalate during late gestation. Toxicological Sciences. 2000;55(1):143-51.
21. Brouwer A Ahlborg U van Leeuwen F Feeley M. Report of the WHO working group on the assessment of health risks for human infants from exposure to PCDDs PCDFs and PCBs. Chemosphere. 1998;37(9-12):1627-43.
22. Li Y Duan F Yang F Zhou X Pan H Li Y Li R. Pubertal exposure to bisphenol A affects the reproduction of male mice and sex ratio of offspring. Journal of Reproduction and Contraception; 2015;14-21; DOI:10.7669/j.issn.1001-7844.2015.01.0014.
23. Wright C Milne S Leeson H. 2014. Sperm DNA damage caused by oxidative stress: modofiable clinical lifestyle and nutritional factors in male infertility Reproductive BioMedicine online 28 (6): 684-703; DOI:10.1016/j.rbmo.2014.02.004.
24. Wang D Gao H Bandyopadhyay A Wu A Yeh I Chen Y Zou Y Huang CJ Walter CA Dong QX Sun LZ. Pubertal Bisphenol A Exposure Alters Murine Mammary Stem Cell Function Leading to Early Neoplasia in Regenerated Glands. Cancer Prevention Research. 2014;7(4):445-55; DOI:10.1158/1940-6207.CAPR-13-0260.
25. Kalb A Kalb A Cardoso T Fernandes C Corcini C Varela A Martinez PE. Maternal Transfer of Bisphenol A During Nursing Causes Sperm Impairment in Male Offspring. Archives of Environmental Contamination and Toxicology. 2016;70(4):793-801; DOI:10.1007/s00244-015-0199-7.
26. Wang H Liu M Li N Luo T Zheng L Zeng X. Bisphenol A Impairs Mature Sperm Functions by a CatSper-Relevant Mechanism. Toxicological Sciences. 2016;152(1):145-54; DOI:10.1093/toxsci/kfw070.