Bisphenol a and reproductive health: update of experimental and human evidence, 2007-2013

Jackye Peretz, Lisa Vrooman, William A Ricke, Patricia A Hunt, Shelley Ehrlich, Russ Hauser, Vasantha Padmanabhan, Hugh S Taylor, Shanna H Swan, Catherine A VandeVoort, Jodi A Flaws, Jackye Peretz, Lisa Vrooman, William A Ricke, Patricia A Hunt, Shelley Ehrlich, Russ Hauser, Vasantha Padmanabhan, Hugh S Taylor, Shanna H Swan, Catherine A VandeVoort, Jodi A Flaws

Abstract

Background: In 2007, an expert panel reviewed associations between bisphenol A (BPA) exposure and reproductive health outcomes. Since then, new studies have been conducted on the impact of BPA on reproduction.

Objective: In this review, we summarize data obtained since 2007, focusing on a) findings from human and animal studies, b) the effects of BPA on a variety of reproductive end points, and c) mechanisms of BPA action.

Methods: We reviewed the literature published from 2007 to 2013 using a PubMed search based on keywords related to BPA and male and female reproduction.

Discussion: Because BPA has been reported to affect the onset of meiosis in both animal and in vitro models, interfere with germ cell nest breakdown in animal models, accelerate follicle transition in several animal species, alter steroidogenesis in multiple animal models and women, and reduce oocyte quality in animal models and women undergoing in vitro fertilization (IVF), we consider it an ovarian toxicant. In addition, strong evidence suggests that BPA is a uterine toxicant because it impaired uterine endometrial proliferation, decreased uterine receptivity, and increased implantation failure in animal models. BPA exposure may be associated with adverse birth outcomes, hyperandrogenism, sexual dysfunction, and impaired implantation in humans, but additional studies are required to confirm these associations. Studies also suggest that BPA may be a testicular toxicant in animal models, but the data in humans are equivocal. Finally, insufficient evidence exists regarding effects of BPA on the oviduct, the placenta, and pubertal development.

Conclusion: Based on reports that BPA impacts female reproduction and has the potential to affect male reproductive systems in humans and animals, we conclude that BPA is a reproductive toxicant.

Conflict of interest statement

The authors declare they have no actual or potential competing financial interests.

References

    1. Adewale HB, Jefferson WN, Newbold RR, Patisaul HB. Neonatal bisphenol-A exposure alters rat reproductive development and ovarian morphology without impairing activation of gonadotropin-releasing hormone neurons. Biol Reprod. 2009;81:690–699.
    1. Aghajanova L, Giudice LC. Effect of bisphenol A on human endometrial stromal fibroblasts in vivo. Reprod Biomed Online. 2011;22:249–256.
    1. Aldad TS, Rahmani N, Leranth C, Taylor HS. Bisphenol-A exposure alters endometrial progesterone receptor expression in the nonhuman primate. Fertil Steril. 2011;96:175–179.
    1. An BS, Ahn HJ, Kang HS, Jung EM, Yang H, Hong EJ, et al. Effects of estrogen and estrogenic compounds, 4-tert-octylphenol, and bisphenol A on the uterine contraction and contraction-associated proteins in rats. Mol Cell Endocrinol. 2013;375:27–34.
    1. Anjum S, Rahman S, Kaur M, Ahmad F, Rashid H, Ansari RA, et al. Melatonin ameliorates bisphenol A-induced biochemical toxicity in testicular mitochondria of mouse. Food Chem Toxicol. 2011;49:2849–2854.
    1. Arase S, Ishii K, Igarashi K, Aisaki K, Yoshio Y, Matsushima A, et al. Endocrine disrupter bisphenol A increases in situ estrogen production in the mouse urogenital sinus. Biol Reprod. 2011;84(4):734–742.
    1. Benachour N, Aris A. Toxic effects of low doses of bisphenol-A on human placental cells. Toxicol Appl Pharmacol. 2009;241:322–328.
    1. Berger RG, Foster WG, DeCatanzaro D. Bisphenol-A exposure during the period of blastocyst implantation alters uterine morphology and perturbs measures of estrogen and progesterone receptor expression in mice. Reprod Toxicol. 2010;30:393–400.
    1. Berger RG, Shaw J, deCatanzaro D. Impact of acute bisphenol-A exposure upon intrauterine implantation of fertilized ova and urinary levels of progesterone and 17β-estradiol. Reprod Toxicol. 2008;26:94–99.
    1. Bloom MS, Kim D, vom Saal FS, Taylor JA, Cheng G, Lamb JD, et al. Bisphenol A exposure reduces the estradiol response to gonadotropin stimulation during in vivo fertilization. Fertil Steril. 2011a;96:672–677.
    1. Bloom MS, vom Saal FS, Kim D, Taylor JA, Lamb JD, Fujimoto VY. Serum unconjugated bisphenol A concentrations in men may influence embryo quality indicators during in vivo fertilization. Environ Toxicol Pharmacol. 2011b;32:319–323.
    1. Bosquiazzo VL, Varayoud J, Munoz-de-Toro M, Luque EH, Ramos JG. Effects of neonatal exposure to bisphenol A on steroid regulation of vascular endothelial growth factor expression and endothelial cell proliferation in the adult rat uterus. Biol Reprod. 2010;82:86–95.
    1. Bredhult C, Sahlin L, Olovsson M. Gene expression analysis of human endometrial endothelial cells exposed to bisphenol A. Reprod Toxicol. 2009;28:18–25.
    1. Brieño-Enriquez MA, Reig-Viader R, Cabero L, Toran N, Martinez F, Roig I, et al. Gene expression is altered after bisphenol A exposure in human fetal oocytes in vitro. Mol Hum Reprod. 2012;18:171–183.
    1. Brieño-Enriquez MA, Robles P, Camats-Tarruella N, Garcia-Cruz R, Roig I, Cabero L, et al. Human meiotic progression and recombination are affected by bisphenol A exposure during in vitro human oocyte development. Hum Reprod. 2011;26:2807–2818.
    1. Bromer JG, Zhou Y, Taylor MB, Doherty L, Taylor HS. Bisphenol-A exposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response. FASEB J. 2010;24:2273–2280.
    1. Buck Louis GM, Peterson CM, Chen Z, Croughan M, Sundaram R, Stanford J, et al. Bisphenol A and phthalates and endometriosis: the Endometriosis: Natural History, Diagnosis and Outcomes Study. Fertil Steril. 2013;100:162–169.
    1. Cabaton NJ, Wadia PR, Rubin BS, Zalko D, Schaeberle CM, Askenase MH, et al. 2011Perinatal exposure to environmentally relevant levels of bisphenol A decreases fertility and fecundity in CD-1 mice. Environ Health Perspect 119547–552.; 10.1289/ehp.1002559
    1. Cantonwine D, Meeker JD, Hu H, Sánchez BN, Lamadrid-Figueroa H, Mercado-García A, et al. 2010Bisphenol A exposure in Mexico City and risk of prematurity: a pilot nested case control study. Environ Health 962; 10.1186/1476-069X-9-62
    1. Castro B, Sánchez P, Torres JM, Preda O, del Moral RG, Ortega E.2013Bisphenol A exposure during adulthood alters expression of aromatase and 5α-reductase isozymes in rat prostate. PLoS One 82e55905; 10.1371/journal.pone.0055905
    1. Chao HH, Zhang XF, Chen B, Pan B, Zhang LJ, Li L, et al. Bisphenol A exposure modifies methylation of imprinted genes in mouse oocytes via the estrogen receptor signaling pathway. Histochem Cell Biol. 2012;137:249–259.
    1. Chitra KC, Latchoumycandane C, Mathur PP. Induction of oxidative stress by bisphenol A in the epididymal sperm of rats. Toxicology. 2003;185:119–127.
    1. Chou WC, Chen JL, Lin CF, Chen YC, Shih FC, Chuang CY.2011Biomonitoring of bisphenol A concentrations in maternal and umbilical cord blood in regard to birth outcomes and adipokine expression: a birth cohort study in Taiwan. Environ Health 1094; 10.1186/1476-069X-10-94
    1. Cobellis L, Colacurci N, Trabucco E, Carpentiero C, Grumetto L. Measurement of bisphenol A and bisphenol B levels in human blood sera from healthy and endometriotic women. Biomed Chromatogr. 2009;23:1186–1190.
    1. D’Cruz SC, Jubendradass R, Jayakanthan M, Rani SJ, Mathur PP. Bisphenol A impairs insulin signaling and glucose homeostasis and decreases steroidogenesis in rat testis: an in vivo and in silico study. Food Chem Toxicol. 2012a;50(3–4):1124–1133.
    1. D’Cruz SC, Jubendradass R, Mathur PP. Bisphenol A induces oxidative stress and decreases levels of insulin receptor substrate 2 and glucose transporter 8 in rat testis. Reprod Sci. 2012b;19:163–172.
    1. deCatanzaro D, Berger RG, Guzzo AC, Thorpe JB, Khan A. Perturbation of male sexual behavior in mice (Mus musculus) within a discrete range of perinatal bisphenol-A doses in the context of a high- or low-phytoestrogen diet. Food Chem Toxicol. 2013;55:164–171.
    1. De Flora S, Micale RT, La Maestra S, Izzotti A, D’Agostini F, Camoirano A, et al. Upregulation of clusterin in prostate and DNA damage in spermatozoa from bisphenol A-treated rats and formation of DNA adducts in cultured human prostatic cells. Toxicol Sci. 2011;122:45–51.
    1. Dobrzynska MM, Radzikowska J. Genotoxicity and reproductive toxicity of bisphenol A and X-ray/bisphenol A combination in male mice. Drug Chem Toxicol. 2013;36:19–26.
    1. Ehrlich S, Calafat AM, Humblet O, Smith T, Hauser R. Handling of thermal receipts as a source of exposure to bisphenol A. JAMA. 2014;311:859–60.
    1. Ehrlich S, Williams PL, Hauser R, Missmer SA, Peretz J, Calafat AM, et al. Urinary bisphenol A concentrations and cytochrome P450 19 A1 (Cyp19) gene expression in ovarian granulosa cells: an in vivo human study. Reprod Toxicol. 2013;42:18–23.
    1. Ehrlich S, Williams PL, Missmer SA, Flaws JA, Berry KF, Calafat AM, et al. 2012aUrinary bisphenol A concentrations and implantation failure among women undergoing in vitro fertilization. Environ Health Perspect 120978–983.; 10.1289/ehp.1104307
    1. Ehrlich S, Williams PL, Missmer SA, Flaws JA, Ye X, Calafat AM, et al. Urinary bisphenol A concentrations and early reproductive health outcomes among women undergoing IVF. Hum Reprod. 2012b;27:3583–3592.
    1. Eichenlaub-Ritter U, Vogt E, Cukurcam S, Sun F, Pacchierotti F, Parry J. Exposure of mouse oocytes to bisphenol A causes meiotic arrest but not aneuploidy. Mutat Res. 2008;651:82–92.
    1. El Beshbishy HA, Aly HA, El Shafey M.2012Lipoic acid mitigates bisphenol A-induced testicular mitochondrial toxicity in rats. Toxicol Ind Health; 10.1177/0748233712446728
    1. Fang Y, Zhou Y, Zhong Y, Gao X, Tan T. Effect of vitamin E on reproductive functions and anti-oxidant activity of adolescent male mice exposed to bisphenol A. Wei Sheng Yan Jiu. 2013;42:18–22. [in Chinese]
    1. Fenichel P, Dechaux H, Harthe C, Gal J, Ferrari P, Pacini P, et al. Unconjugated bisphenol A cord blood levels in boys with descended or undescended testes. Hum Reprod. 2012;27:983–990.
    1. Fernández M, Bianchi M, Lux-Lantos V, Libertun C.2009Neonatal exposure to bisphenol A alters reproductive parameters and gonadotropin releasing hormone signaling in female rats. Environ Health Perspect 117757–762.; 10.1289/ehp.0800267
    1. Fernández M, Bourguignon N, Lux-Lantos V, Libertun C.2010Neonatal exposure to bisphenol A and reproductive and endocrine alterations resembling the polycystic ovarian syndrome in adult rats. Environ Health Perspect 1181217–1222.; 10.1289/ehp.0901257
    1. Fujimoto VY, Kim D, vom Saal FS, Lamb JD, Taylor JA, Bloom MS. Serum unconjugated bisphenol A concentrations in women may adversely influence oocyte quality during in vivo fertilization. Fertil Steril. 2011;95:1816–1819.
    1. Galloway T, Cipelli R, Guralnik J, Ferrucci L, Bandinelli S, Corsi AM, et al. 2010Daily bisphenol A excretion and associations with sex hormone concentrations: results from the InCHIANTI adult population study. Environ Health Perspect 1181603–1608.; 10.1289/ehp.1002367
    1. Gayrard V, Lacroix MZ, Collet SH, Viguié C, Bousquet-Melou A, Toutain PL, et al. 2013High bioavailability of bisphenol A from sublingual exposure. Environ Health Perpect 121951–956.; 10.1289/ehp.1206339
    1. Grasselli F, Baratta L, Baioni L, Bussolati S, Ramoni R, Grolli S, et al. Bisphenol A disrupts granulosa cell function. Domest Anim Endocrinol. 2010;39:34–39.
    1. Hampton T. NIH panel: name change, new priorities advised for polycystic ovary syndrome. JAMA. 2013;309:863.
    1. Hiyama M, Choi EK, Wakitani S, Tachibana T, Khan H, Kusakabe KT, et al. Bisphenol-A (BPA) affects reproductive formation across generations in mice. J Vet Med Sci. 2011;73:1211–1215.
    1. Horstman KA, Naciff JM, Overmann GJ, Foertsch LM, Richardson BD, Daston GP. Effects of transplacental 17-α-ethynyl estradiol or bisphenol A on the developmental profile of steroidogenic acute regulatory protein in the rat testis. Birth Defects Res B Dev Reprod Toxicol. 2012;95(4):318–325.
    1. Howdeshell KL, Furr J, Lambright CR, Wilson VS, Ryan BC, Gray LE., Jr Gestational and lactational exposure to ethinyl estradiol, but not bisphenol A, decreases androgen-dependent reproductive organ weights and epididymal sperm abundance in the male Long Evans hooded rat. Toxicol Sci. 2008;102:371–382.
    1. Hunt PA, Koehler KE, Susiarjo M, Hodges CA, Illagan A, Voigt RC, et al. Bisphenol A exposures causes meiotic aneuploidy in the female mouse. Curr Biol. 2003;13:546–553.
    1. Hunt PA, Lawson C, Gieske M, Murdoch B, Smith H, Marre A, et al. Bisphenol A alters early oogenesis and follicle formation in the fetal ovary of the rhesus monkey. Proc Natl Acad Sci USA. 2012;109:17525–17530.
    1. Hunt PA, Susiarjo M, Rubio C, Hassold TJ. The bisphenol A experience: a primer for the analysis of environmental effects on mammalian reproduction. Biol Reprod. 2009;81(5):807–813.
    1. Iguchi T, Fukazawa Y, Uesugi Y, Taksugi N. Polyovular follicles in mouse ovaries exposed neonatally to diethylstilbestrol in vivo and in vitro. Biol Reprod. 1990;43:478–484.
    1. Jin P, Wang X, Chang F, Bai Y, Li Y, Zhou R, et al. Low dose bisphenol A impairs spermatogenesis by suppressing reproductive hormone production and promoting germ cell apoptosis in adult rats. J Biomed Res. 2013;27:135–144.
    1. Kabuto H, Amakawa M, Shishibori T. Exposure to bisphenol A during embryonic/fetal life and infancy increases oxidative injury and cause underdevelopment of the brain and testes in mice. Life Sci. 2004;30:2931–2940.
    1. Kabuto H, Hasuike S, Minagawa N, Shishibori T. Effects of bisphenol A on the metabolisms of active oxygen species in mouse tissues. Environ Res. 2003;93:31–35.
    1. Kandaraki E, Chatzigeorgiou A, Livadas S, Palioura E, Economou F, Koutsilieris M, et al. Endocrine disruptors and polycystic ovary syndrome (PCOS): elevated serum levels of bisphenol A in women with PCOS. J Clin Endocrinol Metab. 2011;96:E480–E484.
    1. Kobayashi K, Kubota H, Ohtani K, Hojo R, Miyagawa M. Lack of effects for dietary exposure of bisphenol A during in utero and lactational periods on reproductive development in rat offspring. J Toxicol Sci. 2012;37:565–573.
    1. Kobayashi K, Ohtani K, Kubota H, Miyagawa M. Dietary exposure to low doses of bisphenol A: effects on reproduction and development in two generations of C57BL/6J mice. Congenit Anom (Kyoto) 2010;50:159–170.
    1. 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;92:526–533.
    1. Lawson C, Gieske M, Murdoch B, Ye P, Li Y, Hassold T, et al. Gene expression in the fetal mouse ovary is altered by exposure to low doses of bisphenol A. Biol Reprod. 2011;84:79–86.
    1. Lee BE, Park H, Hong YC, Ha M, Kim Y, Chang N, et al. 2014Prenatal bisphenol A and birth outcomes: MOCEH (Mothers and Children’s Environmental Health) study. Int J Hyg Environ Health 2172–3328–334.; 10.1016/j.ijheh.2013.07.005
    1. Lee SG, Kim JY, Chung JY, Kim YJ, Park JE, Oh S, et al. 2013Bisphenol A exposure during adulthood causes augmentation of follicular atresia and luteal regression by decreasing 17β-estradiol synthesis via downregulation of aromatase in rat ovary. Environ Health Perspect 121663–669.; 10.1289/ehp.1205823
    1. Lee SH, Kang SM, Choi MH, Lee J, Park MJ, Kim SH, Lee WY, Hong J, Chung BC.2014Changes in steroid metabolism among girls with precocious puberty may not be associated with urinary levels of bisphenol A. Reprod Toxicol 441–6.; 10.1016/j.reprotox.2013.03.008
    1. Lenie S, Cortvrindt R, Eichenlaub-Ritter U, Smitz J. Continuous exposure to bisphenol A during in vivo follicular development induces meiotic abnormalities. Mutat Res. 2008;651:71–81.
    1. Li DK, Zhou Z, Miao M, He Y, Wang J, Ferber J, et al. Urine bisphenol-A (BPA) level in relation to semen quality. Fertil Steril. 2011;95:625–630.
    1. Li DK, Zhou Z, Qing D, He Y, Wu T, Miao M, et al. Occupational exposure to bisphenol-A (BPA) and the risk of self-reported male sexual dysfunction. Hum Reprod. 2010;25:519–527.
    1. Li Y, Zhang W, Liu J, Wang W, Li H, Zhu J, et al. 2014Prepubertal bisphenol A exposure interferes with ovarian follicle development and its relevant gene expression. Reprod Toxicol 4433–40.; 10.1016/j.reprotox.2013.09.002
    1. Li YJ, Song TB, Cai YY, Zhou JS, Song X, Zhao X, et al. Bisphenol A exposure induces apoptosis and upregulation of Fas/FasL and caspase-3 expression in the testes of mice. Toxicol Sci. 2009;108(2):427–436.
    1. Liu C, Duan W, Li R, Xu S, Zhang L, Chen C, et al. 2013Exposure to bisphenol A disrupts meiotic progression during spermatogenesis in adult rats through estrogen-like activity. Cell Death Dis 4e676; 10.1038/cddis.2013.203
    1. Machtinger R, Combelles CM, Missmer SA, Correia KF, Williams P, Hauser R, et al. Bisphenol-A and human oocyte maturation in vitro. Hum Reprod. 2013;28:2735–2745.
    1. Meeker JD, Calafat AM, Hauser R. Urinary bisphenol A concentrations in relation to serum thyroid and reproductive hormone levels in men from an infertility clinic. Environ Sci Technol. 2010a;44:1458–1463.
    1. Meeker JD, Ehrlich S, Toth TL, Wright DL, Calafat AM, Trisini AT, et al. Semen quality and sperm DNA damage in relation to urinary bisphenol A among men from an infertility clinic. Reprod Toxicol. 2010b;30:532–539.
    1. Mendiola J, Jørgensen N, Andersson AM, Calafat AM, Ye X, Redmon JB, et al. 2010Are environmental levels of bisphenol A associated with reproductive function in fertile men? Environ Health Perspect 1181286–1291.; 10.1289/ehp.1002037
    1. Mendoza-Rodríguez CA, García-Guzmán M, Baranda-Avila N, Morimoto S, Perrot-Applanat M, Cerbón M. Administration of bisphenol A to dams during perinatal period modifies molecular and morphological reproductive parameters of the offspring. Reprod Toxicol. 2011;31:177–183.
    1. 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. 2011a;91:867–872.
    1. Miao M, Yuan W, Zhu G, He X, Li DK. In utero exposure to bisphenol-A and its effect on birth weight of offspring. Reprod Toxicol. 2011b;32:64–68.
    1. Minamiyama Y, Ichikawa H, Takemura S, Kusunoki H, Naito Y, Yoshikawa T. Generation of reactive oxygen species in sperms of rats as an earlier marker for evaluating the toxicity of endocrine-disrupting chemicals. Free Radic Res. 2010;44(12):1398–1406.
    1. Mok-Lin E, Ehrlich S, Williams PL, Petrozza J, Wright DL, Calafat AM, et al. Urinary bisphenol A concentrations and ovarian response among women undergoing IVF. Int J Androl. 2010;33:385–393.
    1. Morice L, Benaîtreau D, Dieudonné MN, Morvan C, Serazin V, de Mazancourt P, et al. Antiproliferative and proapoptotic effects of bisphenol A on human trophoblastic JEG-3 cells. Reprod Toxicol. 2011;32:69–76.
    1. Muhlhauser A, Susiarjo M, Rubio C, Griswold J, Gorence G, Hassold T, et al. 2009Bisphenol A effects on the growing mouse oocyte are influenced by diet. Biol Reprod 801067–1072.; 10.1095/biolreprod.108.074815
    1. Nah WH, Park MJ, Gye MC. Effects of early prepubertal exposure to bisphenol A on the onset of puberty, ovarian weights, and estrous cycle in female mice. Clin Exp Reprod Med. 2011;38:75–81.
    1. Nakamura D, Yanagiba Y, Duan Z, Ito Y, Okamura A, Asaeda N, et al. Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol. Toxicol Lett. 2010;194:16–25.
    1. Nanjappa MK, Simon L, Akingbemi BT. 2012The industrial chemical bisphenol A (BPA) interferes with proliferative activity and development of steroidogenic capacity in rat Leydig cells. Biol Reprod 865135, 1–12.; 10.1095/biolreprod.111.095349
    1. Newbold RR, Jefferson WN, Padilla-Banks E.2009Prenatal exposure to bisphenol A at environmentally relevant doses adversely affects the murine female reproductive tract later in life. Environ Health Perspect 117879–885.; 10.1289/ehp.0800045
    1. Nicholson TM, Ricke EA, Marker PC, Miano JM, Mayer RD, Timms BG, et al. Testosterone and 17β-estradiol induce glandular prostatic growth, bladder outlet obstruction, and voiding dysfunction in male mice. Endocrinology. 2012;153(11):5556–5565.
    1. Nicholson TM, Ricke WA. Androgens and estrogens in benign prostatic hyperplasia: past, present and future. Differentiation. 2011;82(4–5):184–199.
    1. N’Tumba-Byn T, Moison D, Lacroix M, Lecureuil C, Lesage L, Prud’homme SM, et al. 2013Differential effects of bisphenol A and diethylstilbestrol on human, rat and mouse fetal Leydig cell function. PLoS One 712e51579; 10.1371/journal.pone.0051579
    1. Okada A, Kai O. Effects of estradiol-17beta and bisphenol A administered chronically to mice throughout pregnancy and lactation on the male pups’ reproductive system. Asian J Androl. 2008;10:271–276.
    1. Pacchierotti F, Ranaldi R, Eichenlaub-Ritter U, Attia S, Adler ID. Evaluation of aneugenic effects of bisphenol A in somatic and germ cells of the mouse. Mutat Res. 2008;651:64–70.
    1. Padmanabhan V, Siefert K, Ransom S, Johnson T, Pinkerton J, Anderson L, et al. Maternal bisphenol-A levels at delivery: a looming problem? J Perinatol. 2008;28:258–263.
    1. Peretz J, Craig ZR, Flaws JA.2012Bisphenol A inhibits follicle growth and induces atresia in cultured mouse antral follicles independently of the genomic estrogenic pathway. Biol Reprod 87363; 10.1095/biolreprod.112.101899
    1. Peretz J, Gupta RK, Singh J, Hernandez-Ochoa I, Flaws JA. Bisphenol A impairs follicle growth, inhibits steroidogenesis, and downregulates rate-limiting enzymes in the estradiol biosynthesis pathway. Toxicol Sci. 2011;119:209–217.
    1. Philippat C, Mortamais M, Chevrier C, Petit C, Calafat AM, Ye X, et al. 2012Exposure to phthalates and phenols during pregnancy and offspring size at birth. Environ Health Perspect 120464–470.; 10.1289/ehp.1103634
    1. Prins GS, Ye SH, Birch L, Ho SM, Kannan K. Serum bisphenol A pharmacokinetics and prostate neoplastic responses following oral and subcutaneous exposures in neonatal Sprague-Dawley rats. Reprod Toxicol. 2011;31:1–9.
    1. Qiao L, Zheng L, Cai D. Study on the levels of the bisphenol A, octylphenol, 4-nonylphenol in serum of precocious girls. Wei Sheng Yan Jiu. 2010;39(1):9–12. [in Chinese]
    1. Qiu LL, Wang X, Zhang XH, Zhang Z, Gu J, Liu L, et al. Decreased androgen receptor expression may contribute to spermatogenesis failure in rats exposed to low concentration of bisphenol A. Toxicol Lett. 2013;219:116–124.
    1. Rashid H, Ahmad F, Rahman S, Ansari RA, Bhatia K, Kaur M, et al. Iron deficiency augments bisphenol A-induced oxidative stress in rats. Toxicology. 2009;256:7–12.
    1. Richter CA, Birnbaum LS, Farabollini F, Newbold RR, Rubin BS, Talsness CE, et al. In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol. 2007;24(2):199–224.
    1. Ricke WA, McPherson SJ, Bianco JJ, Cunha GR, Wang Y, Risbridger GP. Prostatic hormonal carcinogenesis is mediated by in situ estrogen production and estrogen receptor alpha signaling. FASEB J. 2008;22(5):1512–1520.
    1. Rivera OE, Varayoud J, Rodriguez HA, Munoz-de-Toro M, Luque EH. Neonatal exposure to bisphenol A or diethylstilbestrol alters the ovarian follicular dynamics in the lamb. Reprod Toxicol. 2011;32:304–312.
    1. Rodríguez HA, Santambrosio N, Santamaría CG, Muñoz-de-Toro M, Luque EH. Neonatal exposure to bisphenol A reduces the pool of primordial follicles in the rat ovary. Reprod Toxicol. 2010;2010;30:550–557.
    1. Ross C, Morriss A, Khairy M, Khalaf Y, Braude P, Coomarasamy A, et al. A systematic review of the effect of oral antioxidants on male infertility. Reprod Biomed Online. 2010;20(6):711–723.
    1. Ryan BC, Hotchkiss AK, Crofton KM, Gray LE., Jr In utero and lactational exposure to bisphenol A, in contrast to ethinyl estradiol, does not alter sexually dimorphic behavior, puberty, fertility, and anatomy of female LE rats. Toxicol Sci. 2010;114:133–148.
    1. Salian S, Doshi T, Vanage G. Neonatal exposure of male rats to bisphenol A impairs fertility and expression of Sertoli cell junctional proteins in the testis. Toxicology. 2009a;265:56–67.
    1. Salian S, Doshi T, Vanage G. Perinatal exposure of rats to bisphenol A affects the fertility of male offspring. Life Sci. 2009b;85:742–752.
    1. Sánchez P, Castro B, Torres JM, Olmo A, del Moral RG, Ortega E.2013Bisphenol A modifies the regulation exerted by testosterone on 5α-reductase isozymes in ventral prostate of adult rats. Biomed Res Int 2013629235; 10.1155/2013/629235
    1. Signorile PG, Spugnini EP, Mita L, Mellone P, D’Avino A, Bianco M, et al. Pre-natal exposure of mice to bisphenol A elicits an endometriosis-like phenotype in female offspring. Gen Comp Endocrinol. 2010;168:318–325.
    1. Snijder CA, Heederik D, Pierik FH, Hofman A, Jaddoe VW, Koch HM, et al. 2013Fetal growth and prenatal exposure to bisphenol A: the generation R Study. Environ Health Perspect 121393–398.; 10.1289/ehp.1205296
    1. Susiarjo M, Hassold TJ, Freeman E, Hunt PA.2007Bisphenol A exposure in utero disrupts early oogenesis in the mouse. PLoS Genet 31e5; 10.1371/journal.pgen.0030005
    1. Susiarjo M, Sasson I, Mesaros C, Bartolomei MS.2013Bisphenol A exposure disrupts genomic imprinting in the mouse. PLoS Genet 94e1003401; 10.1371/journal.pgen.1003401
    1. Tainaka H, Takahashi H, Umezawa M, Tanaka H, Nishimune Y, Oshio S, et al. Evaluation of the testicular toxicity of prenatal exposure to bisphenol A based on microarray analysis combined with MeSH annotation. J Toxicol Sci. 2012;37:539–548.
    1. Tan W, Huang H, Wang Y, Wong TY, Wang CC, Leung LK.2013Bisphenol A differentially activates protein kinase C isoforms in murine placental tissue. Toxicol Appl Pharmacol 2692163–168.; 10.1016/j.taap.2013.03.016
    1. Tang WY, Morey LM, Cheung YY, Birch L, Prins GS, Ho SM. Neonatal exposure to estradiol/bisphenol A alters promoter methylation and expression of Nsbp1 and Hpcal1 genes and transcriptional programs of Dnmt3a/b and Mbd2/4 in the rat prostate gland throughout life. Endocrinology. 2012;153(1):42–55.
    1. Thuillier R, Manku G, Wang Y, Culty M. Changes in MAPK pathway in neonatal and adult testis following fetal estrogen exposure and effects on rat testicular cells. Microsc Res Tech. 2009;72:773–786.
    1. Tiwari D, Vanage G.2013Mutagenic effect of bisphenol A on adult rat male germ cells and their fertility. Reprod Toxicol 4060–68.; 10.1016/j.reprotox.2013.05.013
    1. Trapphoff T, Heiligentag M, El Hajj N, Haaf T, Eichenlaub-Ritter U. 2013Chronic exposure to a low concentration of bisphenol A during follicle culture affects the epigenetic status of germinal vesicles and metaphase II oocytes. Fertil Steril 10061758–1767.e1.; 10.1016/j.fertnstert.2013.08.021
    1. Tyl RW, Myers CB, Marr MC, Sloan CS, Castillo NP, Veselica MM, et al. Two-generation reproductive toxicity study of dietary bisphenol A in CD-1 (Swiss) mice. Toxicol Sci. 2008;104:362–384.
    1. U.S. EPA (U.S. Environmental Protection Agency). Bisphenol A (CASRN 80-05-7). Updated 07/01/1993. Available: [accessed 25 June 2014]
    1. Vandenberg LN, Chahoud I, Heindel JJ, Padmanabhan V, Paumgartten FJ, Schoenfelder G.2010Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A. Environ Health Perspect 1181055–1070.; 10.1289/ehp.0901716
    1. Vandenberg LN, Ehrlich S, Belcher SM, Ben-Jonathan N, Dolinoy DC, Hugo ER, et al. 2013Low dose effects of bisphenol A: An integrated review of in vitro, laboratory animal, and epidemiology studies. Endocr Disruptors 11e25078; 10.4161/endo.26490
    1. Varayoud J, Ramos JG, Bosquiazzo VL, Lower M, Munoz-de-Toro M, Luque EH. Neonatal exposure to bisphenol A alters rat uterine implantation-associated gene expression and reduces the number of implantation sites. Endocrinology. 2011;152:1101–1111.
    1. Varayoud J, Ramos JG, Bosquiazzo VL, Munoz-de-Toro M, Luque EH. Developmental exposure to bisphenol A impairs the uterine response to ovarian steroids in the adult. Endocrinology. 2008;149:5848–5860.
    1. Veiga-Lopez A, Luense LJ, Christenson LK, Padmanabhan V. Developmental programming: gestational bisphenol-A treatment alters trajectory of fetal ovarian gene expression. Endocrinology. 2013;154(5):1873–1884.
    1. vom Saal FS, Akingbemi BT, Belcher SM, Birnbaum LS, Crain DA, Eriksen M, et al. Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure. Reprod Toxicol. 2007;24:131–138.
    1. vom Saal FS, VandeVoort C, Taylor J, Welshons W, Toutain PL, Hunt PA.2014Bisphenol A (BPA) pharmacokinetics with daily oral bolus or continuous exposure via silastic capsules in pregnant rehesus monkeys:relevance for human exposures. Reprod Toxicol 45105–116.; 10.1016/j.reprotox.2014.01.007
    1. Wang Q, Zhao XF, Ji YL, Wang H, Liu P, Zhang C, et al. Mitochondrial signaling pathway is also involved in bisphenol A induced germ cell apoptosis in testes. Toxicol Lett. 2010;199(2):129–135.
    1. Wang Z, Liu BC, Lin GT, Lin CS, Lue TF, Willingham E, et al. Up-regulation of estrogen responsive genes in hypospadias: microarray analysis. J Urol. 2007;177(5):1939–1946.
    1. Willingham E, Baskin LS. Candidate genes and their response to environmental agents in the etiology of hypospadias. Nat Clin Pract Urol. 2007;4(5):270–279.
    1. Wolff MS, Britton JA, Boguski L, Hochman S, Maloney N, Serra N, et al. Environmental exposures and puberty in inner-city girls. Environ Res. 2008a;107(3):393–400.
    1. Wolff MS, Engel SM, Berkowitz GS, Ye X, Silva MJ, Zhu C, et al. 2008bPrenatal phenol and phthalate exposures and birth outcomes. Environ Health Perspect. 11681092–1097.; 10.1289/ehp.11007
    1. Wolff MS, Teitelbaum SL, Pinney SM, Windham G, Liao L, Biro F, et al. 2010Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls. Environ Health Perspect 1181039–1046.; 10.1289/ehp.0901690
    1. Wu HJ, Liu C, Duan WX, Xu SC, He MD, Chen CH, et al. Melatonin ameliorates bisphenol A-induced DNA damage in the germ cells of adult male rats. Mutat Res. 2013;752:57–67.
    1. Wu JH, Jiang XR, Liu GM, Liu XY, He GL, Sun ZY. Oral exposure to low-dose bisphenol A aggravates testosterone-induced benign hyperplasia prostate in rats. Toxicol Ind Health. 2011;27:810–819.
    1. Xi W, Lee CK, Yeung WS, Giesy JP, Wong MH, Zhang X, et al. Effect of perinatal and postnatal bisphenol A exposure to the regulatory circuits at the hypothalamus– pituitary–gonadal axis of CD-1 mice. Reprod Toxicol. 2011;31:409–417.
    1. Xiao S, Diao H, Smith MA, Song X, Ye X. Preimplantation exposure to bisphenol A (BPA) affects embryo transport, preimplantation embryo development, and uterine receptivity in mice. Reprod Toxicol. 2011;32:434–441.
    1. Yigit F, Daglioglu S. Histological changes in the uterus of the hens after embryonic exposure to bisphenol A and diethylstilbestrol. Protoplasma. 2010;247:57–63.
    1. Zhang HQ, Zhang XF, Zhang LJ, Chao HH, Pan B, Feng YM, et al. Fetal exposure to bisphenol A affects the primordial follicle formation by inhibiting the meiotic progression of oocytes. Mol Biol Rep. 2012;39:5651–5657.
    1. Zhang XF, Zhang LJ, Feng YN, Chen B, Feng YM, Liang GJ, et al. Bisphenol A exposure modifies DNA methylation of imprint genes in mouse fetal germ cells. Mol Biol Rep. 2012;39:8621–8628.
    1. Zhou W, Liu J, Liao L, Han S, Liu J. Effect of bisphenol A on steroid hormone production in rat ovarian theca-interstitial and granulosa cells. Mol Cell Endocrinol. 2008;283:12–18.
    1. Ziv-Gal A, Craig ZR, Wang W, Flaws JA.2013Bisphenol A inhibits cultured mouse ovarian follicle growth partially via the aryl hydrocarbon receptor signaling pathway. Reprod Toxicol 4258–67.; 10.1016/j.reprotox.2013.07.022

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