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Reviews in Endocrine and Metabolic Disorders
Published in: Reviews in Endocrine and Metabolic Disorders 4/2015

01-12-2015

Environmental endocrine disruptors: Effects on the human male reproductive system

Authors: M. F. Sweeney, N. Hasan, A. M. Soto, C. Sonnenschein

Published in: Reviews in Endocrine and Metabolic Disorders | Issue 4/2015

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Abstract

Incidences of altered development and neoplasia of male reproductive organs have increased during the last 50 years, as shown by epidemiological data. These data are associated with the increased presence of environmental chemicals, specifically “endocrine disruptors,” that interfere with normal hormonal action. Much research has gone into testing the effects of specific endocrine disrupting chemicals (EDCs) on the development of male reproductive organs and endocrine-related cancers in both in vitro and in vivo models. Efforts have been made to bridge the accruing laboratory findings with the epidemiological data to draw conclusions regarding the relationship between EDCs, altered development and carcinogenesis. The ability of EDCs to predispose target fetal and adult tissues to neoplastic transformation is best explained under the framework of the tissue organization field theory of carcinogenesis (TOFT), which posits that carcinogenesis is development gone awry. Here, we focus on the available evidence, from both empirical and epidemiological studies, regarding the effects of EDCs on male reproductive development and carcinogenesis of endocrine target tissues. We also critique current research methodology utilized in the investigation of EDCs effects and outline what could possibly be done to address these obstacles moving forward.
Literature
1.
Global cancer facts & figures 3rd edn. Am. Cancer Soc Atlanta. 2015.
2.
3.
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.PubMedPubMedCentralCrossRef
4.
Sharpe RM, Skakkebaek NE. Are Oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet. 1993;341(8857):1392–5.PubMedCrossRef
5.
Colborn T, Clement C. Chemically-induced alterations in sexual and functional development: the wildlife/human connection. Princeton: Princeton Scientific Publishing; 1992. p. 1–8.
6.
Colborn T, Vom Saal FS, Soto AM. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect. 1993;101(5):378–84.PubMedPubMedCentralCrossRef
7.
Zoeller RT, Brown TR, Doan LL, Gore AC, Skakkebaek NE, Soto AM, et al. Endocrine-disrupting chemicals and public health protection: A statement of principles from the endocrine society. Endocrinology. 2012;153(9):4097–110.PubMedPubMedCentralCrossRef
8.
Aranda A, Pascual A. Nuclear hormone receptors and gene expression. Physiol Rev. 2001;81(3):1269–304.PubMed
9.
Rouiller-Fabre V, Guerquin MJ, N’Tumba-Byn T, Muczynski V, Moison D, Tourpin S, et al. Nuclear receptors and endocrine disruptors in fetal and neonatal testes: A gapped landscape. Front Endocrinol (Lausanne). 2015;6:58.
10.
Rouiller-Fabre V, Habert R, Livera G. Effects of endocrine disruptors on the human fetal testis. Ann Endocrinol (Paris). 2014;75(2):54–7.CrossRef
11.
Latini G, Scoditti E, Verrotti A, De Felice C, Massaro M. Peroxisome proliferator-activated receptors as mediators of phthalate-induced effects in the male and female reproductive tract: Epidemiological and experimental evidence. PPAR Res. 2008;2008:359267.PubMedPubMedCentralCrossRef
12.
Kelce WR, Stone CR, Laws SC, Gray LE, Kemppainen JA, Wilson EM. Persistent DDT metabolite p, p’-DDE is a potent androgen receptor antagonist. Nature. 1995;375(6532):581–5.PubMedCrossRef
13.
Moriyama K, Tagami T, Akamizu T, Usui T, Saijo M, Kanamoto N, et al. Thyroid hormone action is disrupted by bisphenol a as an antagonist. J Clin Endocrinol Metab. 2002;87(11):5185–90.PubMedCrossRef
14.
Wetherill YB, Fisher NL, Staubach A, Danielsen M, de Vere White RW, Knudsen KE. Xenoestrogen action in prostate cancer: Pleiotropic effects dependent on androgen receptor status. Cancer Res. 2005;65(1):54–65.PubMed
15.
Silva E, Rajapakse N, Kortenkamp A. Something from “nothing”--eight weak estrogenic chemicals combined at concentrations below NOECs produce significant mixture effects. Environ Sci Technol. 2002;36(8):1751–6.PubMedCrossRef
16.
Nagel SC, Vom Saal FS, Thayer KA, Dhar MG, Boechler M, Welshons WV. Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol. Environ Health Perspect. 1997;105(1):70–6.
17.
Soto AM, Brisken C, Schaeberle C, Sonnenschein C. Does cancer start in the womb? Altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors. J Mammary Gland Biol Neoplasia. 2013;18(2):199–208.PubMedPubMedCentralCrossRef
18.
Blair RM, Fang H, Branham WS, Hass BS, Dial SL, Moland CL, et al. The estrogen receptor relative binding affinities of 188 natural and xenochemicals: Structural diversity of ligands. Toxicol Sci. 2000;54(1):138–53.PubMedCrossRef
19.
Usmani KA, Rose RL, Hodgson E. Inhibition and activation of the human liver microsomal and human cytochrome P450 3A4 metabolism of testosterone by deployment-related chemicals. Drug Metab Dispos. 2003;31(4):384–91.PubMedCrossRef
20.
Usmani KA, Cho TM, Rose RL, Hodgson E. Inhibition of the human liver microsomal and human cytochrome P450 1A2 and 3A4 metabolism of estradiol by deployment-related and other chemicals. Drug Metab Dispos. 2006;34(9):1606–14.PubMedCrossRef
21.
22.
Martinez-Arguelles DB, Culty M, Zirkin BR, Papadopoulos V. In utero exposure to di-(2-ethylhexyl) phthalate decreases mineralocorticoid receptor expression in the adult testis. Endocrinology. 2009;150(12):5575–85.PubMedPubMedCentralCrossRef
23.
Prins GS, Tang WY, Belmonte J, Ho SM. Perinatal exposure to oestradiol and bisphenol a alters the prostate epigenome and increases susceptibility to carcinogenesis. Basic Clin Pharmacol Toxicol. 2008;102(2):134–8.PubMedPubMedCentralCrossRef
24.
Pelch KE, Tokar EJ, Merrick BA, Waalkes MP. Differential DNA methylation profile of key genes in malignant prostate epithelial cells transformed by inorganic arsenic or cadmium. Toxicol Appl Pharmacol. 2015;286(3):159–67.PubMedCrossRef
25.
Guerrero-Bosagna C, Settles M, Lucker B, Skinner MK. Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome. PLoS One. 2010;5(9):e13100.PubMedPubMedCentralCrossRef
26.
Wu S, Zhu J, Li Y, Lin T, Gan L, Yuan X, et al. Dynamic epigenetic changes involved in testicular toxicity induced by di-2-(ethylhexyl) phthalate in mice. Basic Clin Pharmacol Toxicol. 2010;106(2):118–23.PubMedCrossRef
27.
Anderson AM, Carter KW, Anderson D, Wise MJ. Coexpression of nuclear receptors and histone methylation modifying genes in the testis: Implications for endocrine disruptor modes of action. PLoS One. 2012;7(4):e34158.PubMedPubMedCentralCrossRef
28.
Clement TM, Savenkova MI, Settles M, Anway MD, Skinner MK. Alterations in the developing testis transcriptome following embryonic vinclozolin exposure. Reprod Toxicol. 2010;30(3):353–64.PubMedPubMedCentralCrossRef
29.
Lopez-Casas PP, Mizrak SC, Lopez-Fernandez LA, Paz M, de Rooij DG, del Mazo J. The effects of different endocrine disruptors defining compound-specific alterations of gene expression profiles in the developing testis. Reprod Toxicol. 2012;33(1):106–15.PubMedCrossRef
30.
Stouder C, Paoloni-Giacobino A. Transgenerational effects of the endocrine disruptor vinclozolin on the methylation pattern of imprinted genes in the mouse sperm. Reproduction. 2010;139(2):373–9.PubMedCrossRef
31.
Stouder C, Paoloni-Giacobino A. Specific transgenerational imprinting effects of the endocrine disruptor methoxychlor on male gametes. Reproduction. 2011;141(2):207–16.PubMedCrossRef
32.
Del-Mazo J, Brieno-Enriquez MA, Garcia-Lopez J, Lopez-Fernandez LA, De-Felici M. Endocrine disruptors, gene deregulation and male germ cell tumors. Int J Dev Biol. 2013;57(2–4):225–39.PubMedCrossRef
33.
Choi JS, Oh JH, Park HJ, Choi MS, Park SM, Kang SJ, et al. MiRNA regulation of cytotoxic effects in mouse Sertoli cells exposed to nonylphenol. Reprod Biol Endocrinol. 2011;9:126.PubMedPubMedCentralCrossRef
34.
Watson CJ, Khaled WT. Mammary development in the embryo and adult: A journey of morphogenesis and commitment. Development. 2008;135(6):995–1003.PubMedCrossRef
35.
Singh M, Jha R, Melamed J, Shapiro E, Hayward SW, Lee P. Stromal androgen receptor in prostate development and cancer. Am J Pathol. 2014;184(10):2598–607.PubMedPubMedCentralCrossRef
36.
37.
Maffini MV, Soto AM, Calabro JM, Ucci AA, Sonnenschein C. The stroma as a crucial target in rat mammary gland carcinogenesis. J Cell Sci. 2004;117(Pt 8):1495–502.PubMedCrossRef
38.
Grossfeld GD, Hayward SW, TLsty TD, Cunha GR. The role of stroma in prostatic carcinogenesis. Endocr Relat Cancer. 1998;5:253–70.CrossRef
39.
Ramos JG, Varayoud J, Sonnenschein C, Soto AM, De Toro Munoz M, Luque EH. Prenatal exposure to low doses of bisphenol A alters the periductal stroma and glandular cell function in the rat ventral prostate. Biol Reprod. 2001;65(4):1271–7.PubMedCrossRef
40.
Vandenberg LN, Maffini MV, Wadia PR, Sonnenschein C, Rubin BS, Soto AM. Exposure to environmentally relevant doses of the xenoestrogen bisphenol-a alters development of the fetal mouse mammary gland. Endocrinology. 2007;148(1):116–27.PubMedPubMedCentralCrossRef
41.
Wadia PR, Cabaton NJ, Borrero MD, Rubin BS, Sonnenschein C, Shioda T, et al. Low-dose BPA exposure alters the mesenchymal and epithelial transcriptomes of the mouse fetal mammary gland. PLoS One. 2013;8(5):e63902.PubMedPubMedCentralCrossRef
42.
Markey CM, Luque EH, De Toro Munoz M, Sonnenschein C, Soto AM. In utero exposure to bisphenol A alters the development and tissue organization of the mouse mammary gland. Biol Reprod. 2001;65(4):1215–23.PubMed
43.
Ko K, Moore RW, Peterson RE. Aryl hydrocarbon receptors in urogenital sinus mesenchyme mediate the inhibition of prostatic epithelial bud formation by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol. 2004;196(1):149–55.PubMedCrossRef
44.
Lew BJ, Manickam R, Lawrence BP. Activation of the aryl hydrocarbon receptor during pregnancy in the mouse alters mammary development through direct effects on stromal and epithelial tissues. Biol Reprod. 2011;84(6):1094–102.PubMedPubMedCentralCrossRef
45.
Hendry 3rd WJ, Weaver BP, Naccarato TR, Khan SA. Differential progression of neonatal diethylstilbestrol-induced disruption of the hamster testis and seminal vesicle. Reprod Toxicol. 2006;21(3):225–40.PubMedCrossRef
46.
Mao Y, Baum B. Tug of war--the influence of opposing physical forces on epithelial cell morphology. Dev Biol. 2015;401(1):92–102.PubMedCrossRef
47.
Kim HY, Varner VD, Nelson CM. Apical constriction initiates new bud formation during monopodial branching of the embryonic chicken lung. Development. 2013;140(15):3146–55.PubMedPubMedCentralCrossRef
48.
49.
Latacha KS, Remond MC, Ramasubramanian A, Chen AY, Elson EL, Taber LA. Role of actin polymerization in bending of the early heart tube. Dev Dyn. 2005;233(4):1272–86.PubMedCrossRef
50.
Barnes C, Speroni L, Quinn KP, Montevil M, Saetzler K, Bode-Animashaun G, et al. From single cells to tissues: Interactions between the matrix and human breast cells in real time. PLoS One. 2014;9(4):e93325.PubMedPubMedCentralCrossRef
51.
Spoerl E, Zubaty V, Raiskup-Wolf F, Pillunat LE. Oestrogen-induced changes in biomechanics in the cornea as a possible reason for keratectasia. Br J Ophthalmol. 2007;91(11):1547–50.PubMedPubMedCentralCrossRef
52.
Hillebrand U, Hausberg M, Lang D, Stock C, Riethmuller C, Callies C, et al. How steroid hormones act on the endothelium--insights by atomic force microscopy. Pflugers Arch. 2008;456(1):51–60.PubMedCrossRef
53.
Lee CY, Liu X, Smith CL, Zhang X, Hsu HC, Wang DY, et al. The combined regulation of estrogen and cyclic tension on fibroblast biosynthesis derived from anterior cruciate ligament. Matrix Biol. 2004;23(5):323–9.PubMedCrossRef
54.
Speroni L, Whitt GS, Xylas J, Quinn KP, Jondeau-Cabaton A, Barnes C, et al. Hormonal regulation of epithelial organization in a three-dimensional breast tissue culture model. Tissue Eng C Methods. 2014;20(1):42–51.CrossRef
55.
Barcus CE, Keely PJ, Eliceiri KW, Schuler LA. Stiff collagen matrices increase tumorigenic prolactin signaling in breast cancer cells. J Biol Chem. 2013;288(18):12722–32.PubMedPubMedCentralCrossRef
56.
Paszek MJ, Zahir N, Johnson KR, Lakins JN, Rozenberg GI, Gefen A, et al. Tensional homeostasis and the malignant phenotype. Cancer Cell. 2005;8(3):241–54.PubMedCrossRef
57.
Martin LJ, Boyd NF. Mammographic density. Potential mechanisms of breast cancer risk associated with mammographic density: Hypotheses based on epidemiological evidence. Breast Cancer Res. 2008;10(1):201.PubMedPubMedCentralCrossRef
58.
Miroshnikova YA, Jorgens DM, Spirio L, Auer M, Sarang-Sieminski AL, Weaver VM. Engineering strategies to recapitulate epithelial morphogenesis within synthetic three-dimensional extracellular matrix with tunable mechanical properties. Phys Biol. 2011;8(2):026013.PubMedPubMedCentralCrossRef
59.
Hoyt K, Castaneda B, Zhang M, Nigwekar P, di Sant’agnese PA, Joseph JV, et al. Tissue elasticity properties as biomarkers for prostate cancer. Cancer Biomark. 2008;4(4–5):213–25.PubMedPubMedCentral
60.
Wang X, Wang J, Liu Y, Zong H, Che X, Zheng W, et al. Alterations in mechanical properties are associated with prostate cancer progression. Med Oncol. 2014;31(3):876.PubMedCrossRef
61.
Thompson PA, Khatami M, Baglole CJ, Sun J, Harris SA, Moon EY, et al. Environmental immune disruptors, inflammation and cancer risk. Carcinogenesis. 2015;36 Suppl 1:S232–53.PubMedCrossRef
62.
Gilbert SF. Ecological developmental biology: Developmental biology meets the real world. Dev Biol. 2001;233(1):1–12.PubMedCrossRef
63.
Weinberg RA. One renegade cell: How cancer begins. New York, NY: Basic Books; 1998.
64.
65.
Soto AM, Sonnenschein C. The tissue organization field theory of cancer: A testable replacement for the somatic mutation theory. Bioessays. 2011;33(5):332–40.PubMedPubMedCentralCrossRef
66.
Herbst AL, Anderson D. Clear cell adenocarcinoma of the vagina and cervix secondary to intrauterine exposure to diethylstilbestrol. Semin Surg Oncol. 1990;6(6):343–6.PubMedCrossRef
67.
Palmer JR, Boggs DA, Hatch EE, Troisi R, Titus-Ernstoff L, Strohsnitter WC, et al. Prenatal DES exposure in relation to breast size. Cancer Causes Control. 2013;24(9):1757–61.PubMedCrossRef
68.
69.
Soto AM, Sonnenschein C. Regulation of cell proliferation: The negative control perspective. Ann N Y Acad Sci. 1991;628:412–8.PubMedCrossRef
70.
Soto AM, Murai JT, Siiteri PK, Sonnenschein C. Control of cell proliferation: Evidence for negative control on estrogen-sensitive T47D human breast cancer cells. Cancer Res. 1986;46(5):2271–5.PubMed
71.
Sonnenschein C, Olea N, Pasanen ME, Soto AM. Negative controls of cell proliferation: Human prostate cancer cells and androgens. Cancer Res. 1989;49(13):3474–81.PubMed
72.
Geck P, Maffini MV, Szelei J, Sonnenschein C, Soto AM. Androgen-induced proliferative quiescence in prostate cancer cells: The role of AS3 as its mediator. Proc Natl Acad Sci U S A. 2000;97(18):10185–90.PubMedPubMedCentralCrossRef
73.
Bruchovsky N, Lesser B, Van Doorn E, Craven S. Hormonal effects on cell proliferation in rat prostate. Vitam Horm. 1975;33:61–102.PubMedCrossRef
74.
Sonnenschein C, Soto AM. Pituitary uterotrophic effect in the estrogen-dependent growth of the rat uterus. J Steroid Biochem. 1978;9(6):533–7.PubMedCrossRef
75.
Vandenberg LN, Wadia PR, Schaeberle CM, Rubin BS, Sonnenschein C, Soto AM. The mammary gland response to estradiol: Monotonic at the cellular level, non-monotonic at the tissue-level of organization? J Steroid Biochem Mol Biol. 2006;101(4–5):263–74.PubMedCrossRef
76.
Schweizer MT, Antonarakis ES, Wang H, Ajiboye AS, Spitz A, Cao H, et al. Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer: Results from a pilot clinical study. Sci Transl Med. 2015;7(269):269ra2.PubMedPubMedCentralCrossRef
77.
Denmeade SR, Isaacs JT. Bipolar androgen therapy: The rationale for rapid cycling of supraphysiologic androgen/ablation in men with castration resistant prostate cancer. Prostate. 2010;70(14):1600–7.PubMedPubMedCentralCrossRef
78.
Gleave M, Goldenberg SL, Bruchovsky N, Rennie P. Intermittent androgen suppression for prostate cancer: Rationale and clinical experience. Prostate Cancer Prostatic Dis. 1998;1(6):289–96.PubMedCrossRef
79.
Vom Saal FS, Timms BG, Montano MM, Palanza P, Thayer KA, Nagel SC, et al. Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses. Proc Natl Acad Sci U S A. 1997;94(5):2056–61.PubMedCrossRef
80.
Alworth LC, Howdeshell KL, Ruhlen RL, Day JK, Lubahn DB, Huang TH, et al. Uterine responsiveness to estradiol and DNA methylation are altered by fetal exposure to diethylstilbestrol and methoxychlor in CD-1 mice: Effects of low versus high doses. Toxicol Appl Pharmacol. 2002;183(1):10–22.PubMedCrossRef
81.
Welshons WV, Nagel SC, Thayer KA, Judy BM, Vom Saal FS. Low-dose bioactivity of xenoestrogens in animals: Fetal exposure to low doses of methoxychlor and other xenoestrogens increases adult prostate size in mice. Toxicol Ind Health. 1999;15(1–2):12–25.PubMedCrossRef
82.
Vandenberg LN. Low-dose effects of hormones and endocrine disruptors. Vitam Horm. 2014;94:129–65.PubMedCrossRef
83.
Lagarde F, Beausoleil C, Belcher SM, Belzunces LP, Emond C, Guerbet M, et al. Non-monotonic dose–response relationships and endocrine disruptors: A qualitative method of assessment. Environ Health. 2015;14:13.PubMedPubMedCentralCrossRef
84.
Vandenberg LN. Non-monotonic dose responses in studies of endocrine disrupting chemicals: Bisphenol a as a case study. Dose Response. 2014;12(2):259–76.PubMedPubMedCentralCrossRef
85.
Bay K, Asklund C, Skakkebaek NE, Andersson A-M. Testicular dysgenesis syndrome: Possible role of endocrine disrupters. Best Pract Res Clin Endocrinol Metab. 2006;20(1):77–90.PubMedCrossRef
86.
Prins GS. Neonatal estrogen exposure induces lobe-specific alterations in adult rat prostate androgen receptor expression. Endocrinology. 1992;130(6):3703–14.PubMed
87.
Saffarini CM, McDonnell-Clark EV, Amin A, Huse SM, Boekelheide K. Developmental exposure to estrogen alters differentiation and epigenetic programming in a human fetal prostate xenograft model. PLoS One. 2015;10(3):e0122290.PubMedPubMedCentralCrossRef
88.
Wu CP, Gu FL. The prostate in eunuchs. Prog Clin Biol Res. 1991;370:249–55.PubMed
89.
Cunha GR, Donjacour AA, Cooke PS, Mee S, Bigsby RM, Higgins SJ, et al. The endocrinology and developmental biology of the prostate. Endocr Rev. 1987;8(3):338–62.PubMedCrossRef
90.
He WW, Kumar MV, Tindall DJ. A frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse. Nucleic Acids Res. 1991;19(9):2373–8.PubMedPubMedCentralCrossRef
91.
Brown TR, Lubahn DB, Wilson EM, Joseph DR, French FS, Migeon CJ. Deletion of the steroid-binding domain of the human androgen receptor gene in one family with complete androgen insensitivity syndrome: Evidence for further genetic heterogeneity in this syndrome. Proc Natl Acad Sci U S A. 1988;85(21):8151–5.PubMedPubMedCentralCrossRef
92.
Takeda H, Lasnitzki I, Mizuno T. Analysis of prostatic bud induction by brief androgen treatment in the fetal rat urogenital sinus. J Endocrinol. 1986;110(3):467–70.PubMedCrossRef
93.
George FW, Wilson JD. Sex determination and differentiation. In: Neill EKAJD, editor. The physiology of reproduction. New York: Raven; 1994. p. 3–29.
94.
95.
Cowin PA, Foster PMD, Risbridger GP. Endocrine disruption in the male. In: Gore AC, editor. Endrocrine-disrupting chemicals: From basic research to clinical practice. Totowa, NJ: Humana Press Inc; 2007. p. 33–62.CrossRef
96.
Jarred RA, Cancilla B, Prins GS, Thayer KA, Cunha GR, Risbridger GP. Evidence that estrogens directly alter androgen-regulated prostate development. Endocrinology. 2000;141(9):3471–7.PubMed
97.
Price D. Normal development of the prostate and seminal vesicles of the rat with a study of experimental postnatal modifications. Am J Anat. 1936;60(1):79–127.CrossRef
98.
Weihua Z, Makela S, Andersson LC, Salmi S, Saji S, Webster JI, et al. A role for estrogen receptor beta in the regulation of growth of the ventral prostate. Proc Natl Acad Sci U S A. 2001;98(11):6330–5.PubMedPubMedCentralCrossRef
99.
Santti R, Newbold RR, Makela S, Pylkkanen L, McLachlan JA. Developmental estrogenization and prostatic neoplasia. Prostate. 1994;24(2):67–78.PubMedCrossRef
100.
Rohrmann S, Nelson WG, Rifai N, Brown TR, Dobs A, Kanarek N, et al. Serum estrogen, but not testosterone, levels differ between black and white men in a nationally representative sample of Americans. J Clin Endocrinol Metab. 2007;92(7):2519–25.PubMedCrossRef
101.
Henderson BE, Bernstein L, Ross RK, Depue RH, Judd HL. The early in utero oestrogen and testosterone environment of blacks and whites: Potential effects on male offspring. Br J Cancer. 1988;57(2):216–8.PubMedPubMedCentralCrossRef
102.
Hayes JH, Barry MJ. Screening for prostate cancer with the prostate-specific antigen test: A review of current evidence. JAMA. 2014;311(11):1143–9.PubMedCrossRef
103.
Dalgaard JB, Giertsen JC. Primary carcinoma of the seminal vesicle. Acta Pathol Microbiol. 1956;39(4):255–67.CrossRef
104.
Katzenwadel A, Wolf P. Androgen deprivation of prostate cancer: Leading to a therapeutic dead end. Cancer Lett. 2015;367(1):12–7.PubMedCrossRef
105.
Ahmed A, Ali S, Sarkar FH. Advances in androgen receptor targeted therapy for prostate cancer. J Cell Physiol. 2014;229(3):271–6.PubMedCrossRef
106.
Finkelstein JS, Lee H, Burnett-Bowie S-AM, Pallais CJ, Yu EW, Borges LF, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369(11):1011–22.PubMedPubMedCentralCrossRef
107.
Driscoll SG, Taylor SH. Effects of prenatal maternal estrogen on the male urogenital system. Obstet Gynecol. 1980;56(5):537–42.PubMed
108.
Tarapore P, Ying J, Ouyang B, Burke B, Bracken B, Ho SM. Exposure to bisphenol a correlates with early-onset prostate cancer and promotes centrosome amplification and anchorage-independent growth in vitro. PLoS One. 2014;9(3):e90332.
109.
Lakshman M, Xu L, Ananthanarayanan V, Cooper J, Takimoto CH, Helenowski I, et al. Dietary genistein inhibits metastasis of human prostate cancer in mice. Cancer Res. 2008;68(6):2024–32.PubMedCrossRef
110.
Prins GS, Hu WY, Shi GB, Hu DP, Majumdar S, Li G, et al. Bisphenol a promotes human prostate stem-progenitor cell self-renewal and increases in vivo carcinogenesis in human prostate epithelium. Endocrinology. 2014;155(3):805–17.
111.
Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean P, Guillette LJ, et al. Male reproductive health and environmental xenoestrogens. Environ Health Perspect. 1996;104 Suppl 4:741–803.PubMedPubMedCentralCrossRef
112.
Zeegers MP, Friesema IH, Goldbohm RA, van den Brandt PA. A prospective study of occupation and prostate cancer risk. J Occup Environ Med. 2004;46(3):271–9.PubMedCrossRef
113.
Prince MM, Ruder AM, Hein MJ, Waters MA, Whelan EA, Nilsen N, et al. Mortality and exposure response among 14,458 electrical capacitor manufacturing workers exposed to polychlorinated biphenyls (PCBs). Environ Health Perspect. 2006;114(10):1508–14.PubMedPubMedCentralCrossRef
114.
Grandjean P, Gronlund C, Kjaer IM, Jensen TK, Sorensen N, Andersson AM, et al. Reproductive hormone profile and pubertal development in 14-year-old boys prenatally exposed to polychlorinated biphenyls. Reprod Toxicol. 2012;34(4):498–503.PubMedPubMedCentralCrossRef
115.
Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, et al. Endocrine-disrupting chemicals: An endocrine society scientific statement. Endocr Rev. 2009;30(4):293–342.PubMedPubMedCentralCrossRef
116.
Koutros S, Beane Freeman LE, Lubin JH, Heltshe SL, Andreotti G, Barry KH, et al. Risk of total and aggressive prostate cancer and pesticide use in the agricultural health study. Am J Epidemiol. 2013;177(1):59–74.PubMedPubMedCentralCrossRef
117.
Leav I, Ho SM, Ofner P, Merk FB, Kwan PW, Damassa D. Biochemical alterations in sex hormone-induced hyperplasia and dysplasia of the dorsolateral prostates of noble rats. J Natl Cancer Inst. 1988;80(13):1045–53.PubMedCrossRef
118.
Ho SM, Tang WY, De Frausto Belmonte J, Prins GS. Developmental exposure to estradiol and bisphenol A increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4. Cancer Res. 2006;66(11):5624–32.PubMedPubMedCentralCrossRef
119.
Brandt JZ, Silveira LT, Grassi TF, Anselmo-Franci JA, Favaro WJ, Felisbino SL, et al. Indole-3-carbinol attenuates the deleterious gestational effects of bisphenol a exposure on the prostate gland of male F1 rats. Reprod Toxicol. 2014;43:56–66.PubMedCrossRef
120.
Boberg J, Johansson HK, Hadrup N, Dreisig K, Berthelsen L, Almstrup K, et al. Perinatal exposure to mixtures of anti-androgenic chemicals causes proliferative lesions in rat prostate. Prostate. 2015;75(2):126–40.PubMedCrossRef
121.
Gray Jr LE, Ostby J, Monosson E, Kelce WR. Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual differentiation of the male rat. Toxicol Ind Health. 1999;15(1–2):48–64.PubMedCrossRef
122.
Ito N, Nagasaki H, Arai M, Makiura S, Sugihara S, Hirao K. Histopathologic studies on liver tumorigenesis induced in mice by technical polychlorinated biphenyls and its promoting effect on liver tumors induced by benzene hexachloride. J Natl Cancer Inst. 1973;51(5):1637–46.PubMed
123.
Ahlborg, U.G., Hanberg, A. and Kenne, K. Risk assessment of polychlorinated biphenyls (PCBs). In Nord. Institute Environmental Medicine Karolinska Institutet, 1992.
124.
Brevini TA, Lonergan P, Cillo F, Francisci C, Favetta LA, Fair T, et al. Evolution of mRNA polyadenylation between oocyte maturation and first embryonic cleavage in cattle and its relation with developmental competence. Mol Reprod Dev. 2002;63(4):510–7.PubMedCrossRef
125.
Cillo F, de Eguileor M, Gandolfi F, Brevini TA. Aroclor-1254 affects mRNA polyadenylation, translational activation, cell morphology, and DNA integrity of rat primary prostate cells. Endocr Relat Cancer. 2007;14(2):257–66.PubMedCrossRef
126.
Dieckmann KP, Pichlmeier U. Clinical epidemiology of testicular germ cell tumors. World J Urol. 2004;22(1):2–14.PubMedCrossRef
127.
128.
Koopman P, Münsterberg A, Capel B, Vivian N, Lovell-Badge R. Expression of a candidate sex-determining gene during mouse testis differentiation. Nature. 1990;348(6300):450–2.PubMedCrossRef
129.
Kassim NM, McDonald SW, Reid O, Bennett NK, Gilmore DP, Payne AP. The effects of pre- and postnatal exposure to the Nonsteroidal antiandrogen Flutamide on testis descent and morphology in the albino swiss rat. J Anat. 1997;190(Pt 4):577–88.PubMedPubMedCentralCrossRef
130.
Klonisch T, Fowler PA, Hombach-Klonisch S. Molecular and genetic regulation of testis descent and external genitalia development. Dev Biol. 2004;270(1):1–18.PubMedCrossRef
131.
132.
Skakkebaek NE, Meyts R-DE, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001;16(5):972–78.PubMedCrossRef
133.
McLachlan JA, Newbold RR, Bullock B. Reproductive tract lesions in male mice exposed prenatally to diethylstilbestrol. Science. 1975;190(4218):991–2.PubMedCrossRef
134.
Mahawong P, Sinclair A, Li Y, Schlomer B, Rodriguez Jr E, Ferretti MM, et al. Prenatal diethylstilbestrol induces malformation of the external genitalia of male and female mice and persistent second-generation developmental abnormalities of the external genitalia in two mouse strains. Differentiation. 2014;88(2–3):51–69.PubMedPubMedCentralCrossRef
135.
Baroni, C., Magrini, U., Martinazzi, M. and Bertoli, G., Testicular Leydig cell tumourigenesis by diethylstilbestrol in the BALB/c mouse: Histologic and histochemical study. Eur J Cancer. 1966.
136.
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. Int J Dev Biol. 2013;57(2–4):255–63.PubMedCrossRef
137.
Bray F, Richiardi L, Ekbom A, Pukkala E, Cuninkova M, Moller H. Trends in testicular cancer incidence and mortality in 22 European countries: Continuing increases in incidence and declines in mortality. Int J Cancer. 2006;118(12):3099–111.PubMedCrossRef
138.
Stevens LC. Spontaneous and experimentally induced testicular teratomas in mice. Cell Differ. 1984;15(2–4):69–74.PubMedCrossRef
139.
Almstrup K, Sonne SB, Hoei-Hansen CE, Ottesen AM, Nielsen JE, Skakkebaek NE, et al. From embryonic stem cells to testicular germ cell cancer-- should we be concerned? Int J Androl. 2006;29(1):211–8.PubMedCrossRef
140.
Peng X, Zeng X, Peng S, Deng D, Zhang J. The association risk of male subfertility and testicular cancer: A systematic review. PLoS One. 2009;4(5):e5591.PubMedPubMedCentralCrossRef
141.
Martin OV, Shialis T, Lester JN, Scrimshaw MD, Boobis AR, Voulvoulis N. Testicular dysgenesis syndrome and the estrogen hypothesis: A quantitative meta-analysis. Environ Health Perspect. 2008;116(2):149–57.PubMedPubMedCentralCrossRef
142.
Strohsnitter WC, Noller KL, Hoover RN, Robboy SJ, Palmer JR, Titus-Ernstoff L, et al. Cancer risk in men exposed in utero to diethylstilbestrol. J Natl Cancer Inst. 2001;93(7):545–51.PubMedCrossRef
143.
Choi H, Kim J, Im Y, Lee S, Kim Y. The association between some endocrine disruptors and hypospadias in biological samples. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2012;47(13):2173–9.PubMedCrossRef
144.
Chevalier N, Brucker-Davis F, Lahlou N, Coquillard P, Pugeat M, Pacini P, et al. A negative correlation between insulin-like peptide 3 and bisphenol a in human cord blood suggests an effect of endocrine disruptors on testicular descent during fetal development. Hum Reprod. 2015;30(2):447–53.PubMedCrossRef
145.
Hardell L, Van Bavel B, Lindstrom G, Carlberg M, Eriksson M, Dreifaldt AC, et al. Concentrations of polychlorinated biphenyls in blood and the risk for testicular cancer. Int J Androl. 2004;27(5):282–90.PubMedCrossRef
146.
McGlynn KA, Quraishi SM, Graubard BI, Weber JP, Rubertone MV, Erickson RL. Persistent organochlorine pesticides and risk of testicular germ cell tumors. J Natl Cancer Inst. 2008;100(9):663–71.PubMedCrossRef
147.
Le Cornet C, Fervers B, Oksbjerg Dalton S, Feychting M, Pukkala E, Tynes T, et al. Testicular germ cell tumours and parental occupational exposure to pesticides: A register-based case–control study in the Nordic countries (NORD-TEST study). Occup Environ Med. 2015;72(11):805–11.PubMedCrossRef
148.
Paoli D, Giannandrea F, Gallo M, Turci R, Cattaruzza MS, Lombardo F, et al. Exposure to polychlorinated biphenyls and hexachlorobenzene, semen quality and testicular cancer risk. J Endocrinol Investig. 2015;38(7):745–52.CrossRef
149.
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(8):1056–61.PubMedPubMedCentralCrossRef
150.
Miao M, Yuan W, He Y, Zhou Z, Wang J, Gao E, et al. In utero exposure to bisphenol-a and anogenital distance of male offspring. Birth Defects Res A Clin Mol Teratol. 2011;91(10):867–72.PubMedCrossRef
151.
Dean A, Sharpe RM. Clinical review: Anogenital distance or digit length ratio as measures of fetal androgen exposure: Relationship to male reproductive development and its disorders. J Clin Endocrinol Metab. 2013;98(6):2230–8.PubMedCrossRef
152.
Ge RS, Chen GR, Tanrikut C, Hardy MP. Phthalate ester toxicity in Leydig cells: Developmental timing and dosage considerations. Reprod Toxicol. 2007;23(3):366–73.PubMedCrossRef
153.
Mylchreest E, Wallace DG, Cattley RC, Foster PM. Dose-dependent alterations in androgen-regulated male reproductive development in rats exposed to Di(n-butyl) phthalate during late gestation. Toxicol Sci. 2000;55(1):143–51.PubMedCrossRef
154.
Perez-Martinez C, Garcia-Iglesias MJ, Ferreras-Estrada MC, Bravo-Moral AM, Espinosa-Alvarez J, Escudero-Diez A. Effects of in-utero exposure to zeranol or diethylstilboestrol on morphological development of the fetal testis in mice. J Comp Pathol. 1996;114(4):407–18.PubMedCrossRef
155.
Brouwer A, Ahlborg UG, van Leeuwen FX, Feeley MM. 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.PubMedCrossRef
156.
National Toxicology Program. Carcinogenesis bioassay of bisphenol a (CAS No. 80-05-7) in F344 rats and B6C3F1 mice (feed study). Natl Toxicol Program Tech Rep Ser. 1982;215:1–116.
157.
Seachrist DD, Bonk KW, Ho SM, Prins GS, Soto AM, Keri RA. A review of the carcinogenic potential of bisphenol A. Reprod Toxicol. 2015;S0890-6238(15):30024–1.
158.
Nanjappa MK, Simon L, Akingbemi BT. The industrial chemical bisphenol a (BPA) interferes with proliferative activity and development of steroidogenic capacity in rat Leydig cells. Biol Reprod. 2012;86(5):135. 1–12.PubMedPubMedCentralCrossRef
159.
LaRocca J, Boyajian A, Brown C, Smith SD, Hixon M. Effects of in utero exposure to bisphenol a or diethylstilbestrol on the adult male reproductive system. Birth Defects Res B Dev Reprod Toxicol. 2011;92(6):526–33.PubMedPubMedCentralCrossRef
160.
Vrooman LA, Oatley JM, Griswold JE, Hassold TJ, Hunt PA. Estrogenic exposure alters the spermatogonial stem cells in the developing testis, permanently reducing crossover levels in the adult. PLoS Genet. 2015;11(1):e1004949.PubMedPubMedCentralCrossRef
161.
Tanaka M, Nakaya S, Katayama M, Leffers H, Nozawa S, Nakazawa R, et al. Effect of prenatal exposure to bisphenol a on the serum testosterone concentration of rats at birth. Hum Exp Toxicol. 2006;25(7):369–73.PubMedCrossRef
162.
Kobayashi K, Miyagawa M, Wang RS, Sekiguchi S, Suda M, Honma T. Effects of in utero and lactational exposure to bisphenol a on somatic growth and anogenital distance in F1 rat offspring. Ind Health. 2002;40(4):375–81.PubMedCrossRef
163.
Murray TJ, Maffini MV, Ucci AA, Sonnenschein C, Soto AM. Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol a exposure. Reprod Toxicol. 2007;23(3):383–90.
164.
Iuanow E, Kettler M, Slanetz PJ. Spectrum of disease in the male breast. AJR Am J Roentgenol. 2011;196(3):W247–59.PubMedCrossRef
165.
Vandenberg LN, Schaeberle CM, Rubin BS, Sonnenschein C, Soto AM. The male mammary gland: A target for the xenoestrogen bisphenol a. Reprod Toxicol. 2013;37:15–23.PubMedPubMedCentralCrossRef
166.
167.
Khan MH, Allerton R, Pettit L. Hormone therapy for breast cancer in men. Clin Breast Cancer. 2015;15(4):245–50.PubMedCrossRef
168.
169.
170.
Maidment SL. Question 2. Which medications effectively reduce pubertal gynaecomastia? Arch Dis Child. 2010;95(3):237–9.PubMedCrossRef
171.
Brinton LA, Cook MB, McCormack V, Johnson KC, Olsson H, Casagrande JT, et al. Anthropometric and hormonal risk factors for male breast cancer: Male breast cancer pooling project results. J Natl Cancer Inst. 2014;106(3):djt465.PubMedPubMedCentralCrossRef
172.
Soto AM, Sonnenschein C. Endocrine disruptors: DDT, endocrine disruption and breast cancer. Nat Rev Endocrinol. 2015;11(9):507–8.PubMedPubMedCentral
173.
McClure J, Higgins CC. Bilateral carcinoma of male breast after estrogen therapy. J Am Med Assoc. 1951;146(1):7–9.PubMedCrossRef
174.
Ruckart PZ, Bove FJ, Shanley 3rd E, Maslia M. Evaluation of contaminated drinking water and male breast cancer at marine corps base camp Lejeune north Carolina: A case control study. Environ Health. 2015;14:74.PubMedPubMedCentralCrossRef
175.
176.
Harrington JM, Stein GF, Rivera RO, de Morales AV. The occupational hazards of formulating oral contraceptives--a survey of plant employees. Arch Environ Health. 1978;33(1):12–5.PubMedCrossRef
177.
Brody SA, Loriaux DL. Epidemic of gynecomastia among Haitian refugees: Exposure to an environmental antiandrogen. Endocr Pract. 2003;9(5):370–5.PubMedCrossRef
178.
179.
Nebesio TD, Eugster EA. Current concepts in normal and abnormal puberty. Curr Probl Pediatr Adolesc Health Care. 2007;37(2):50–72.PubMedCrossRef
180.
Durmaz E, Ozmert EN, Erkekoglu P, Giray B, Derman O, Hincal F, et al. Plasma phthalate levels in pubertal gynecomastia. Pediatrics. 2010;125(1):e122–9.PubMedCrossRef
181.
Delclos KB, Bucci TJ, Lomax LG, Latendresse JR, Warbritton A, Weis CC, et al. Effects of dietary genistein exposure during development on male and female CD (Sprague–Dawley) rats. Reprod Toxicol. 2001;15(6):647–63.PubMedCrossRef
182.
Latendresse JR, Bucci TJ, Olson G, Mellick P, Weis CC, Thorn B, et al. Genistein and Ethinyl estradiol dietary exposure in multigenerational and chronic studies induce similar proliferative lesions in mammary gland of male Sprague–Dawley rats. Reprod Toxicol. 2009;28(3):342–53.PubMedCrossRef
183.
Tate-Ostroff BA, Bridges RS. Nipple development and pup-induced prolactin release in male rats treated prenatally with the antiandrogen Flutamide. Psychoneuroendocrinology. 1988;13(4):309–16.PubMedCrossRef
184.
You L, Sar M, Bartolucci EJ, McIntyre BS, Sriperumbudur R. Modulation of mammary gland development in prepubertal male rats exposed to genistein and methoxychlor. Toxicol Sci. 2002;66(2):216–25.PubMedCrossRef
185.
Wang XJ, Bartolucci-Page E, Fenton SE, You L. Altered mammary gland development in male rats exposed to genistein and methoxychlor. Toxicol Sci. 2006;91(1):93–103.PubMedCrossRef
186.
187.
Soto AM, Sonnenschein C. In: Naz RK, editor. Estrogens, xenoestrogens, and the development of neoplasms in endocrine disruptors: Effects in male and female reproductive systems. Boca Raton: CRC Press; 1999. p. 125–63.
188.
189.
Soto, A. M., Michaelson, C. L., Prechtl, N. L., and Sonnenschein, C., In vitro endocrine disruptor screening. Environmental toxicology and risk assessment. Vol. 8, West Conshohocken, PA: American Society for Testing and Materials; 1999.
190.
Villalobos M, Olea N, Brotons JA, Olea-Serrano MF, De Almodovar Ruiz JM, Pedraza V. The E-screen assay: a comparison of different MCF7 cell stocks. Environ Health Perspect. 1995;103(9):844–50.PubMedPubMedCentralCrossRef
191.
Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs Jr DR, Lee DH, et al. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev. 2012;33(3):378–455.PubMedPubMedCentralCrossRef
192.
Zoeller RT, Bergman A, Becher G, Bjerregaard P, Bornman R, Brandt I, et al. A path forward in the debate over health impacts of endocrine disrupting chemicals. Environ Health. 2015;14:118.CrossRef
193.
Vom Saal FS, Akingbemi BT, Belcher SM, Crain DA, Crews D, Guidice LC, et al. Flawed experimental design reveals the need for guidelines requiring appropriate positive controls in endocrine disruption research. Toxicol Sci. 2010;115(2):612–3. author reply 614–20.PubMedCrossRef
194.
Myers JP, Vom Saal FS, Akingbemi BT, Arizono K, Belcher S, Colborn T, et al. Why public health agencies cannot depend on good laboratory practices as a criterion for selecting data: the case of bisphenol A. Environ Health Perspect. 2009;117(3):309–15.PubMedPubMedCentralCrossRef
195.
N’Tumba-Byn T, Moison D, Lacroix M, Lecureuil C, Lesage L, Prud’homme SM, et al. Differential effects of bisphenol a and diethylstilbestrol on human, rat and mouse fetal Leydig cell function. PLoS One. 2012;7(12):e51579.PubMedPubMedCentralCrossRef
196.
Desdoits-Lethimonier C, Albert O, Le Bizec B, Perdu E, Zalko D, Courant F, et al. Human testis steroidogenesis is inhibited by phthalates. Hum Reprod. 2012;27(5):1451–9.PubMedCrossRef
197.
Delclos KB, Camacho L, Lewis SM, Vanlandingham MM, Latendresse JR, Olson GR, et al. Toxicity evaluation of bisphenol a administered by gavage to Sprague Dawley rats from gestation day 6 through postnatal day 90. Toxicol Sci. 2014;139(1):174–97.PubMedPubMedCentralCrossRef
198.
Vom Saal FS, Welshons WV. Evidence that bisphenol A (BPA) can be accurately measured without contamination in human serum and urine, and that BPA causes numerous hazards from multiple routes of exposure. Mol Cell Endocrinol. 2014;398(1–2):101–13.PubMedCrossRef
199.
Acevedo N, Davis B, Schaeberle CM, Sonnenschein C, Soto AM. Perinatally administered bisphenol a as a potential mammary gland carcinogen in rats. Environ Health Perspect. 2013;121(9):1040–6.PubMedPubMedCentral
Metadata
Title
Environmental endocrine disruptors: Effects on the human male reproductive system
Authors
M. F. Sweeney
N. Hasan
A. M. Soto
C. Sonnenschein
Publication date
01-12-2015
Publisher
Springer US
Published in
Reviews in Endocrine and Metabolic Disorders / Issue 4/2015
Print ISSN: 1389-9155
Electronic ISSN: 1573-2606
DOI
https://doi.org/10.1007/s11154-016-9337-4

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