Bisphenol-A (BPA) Affects Reproductive Formation across Generations in Mice

Hiyama, Masato; Choi, Ehn-Kyong; Wakitani, Shoichi; Tachibana, Toru; Khan, Hamayun; Kusakabe, Ken Takeshi; Kiso, Yasuo

doi:10.1292/jvms.11-0135

Cited by 29 publications

(24 citation statements)

References 16 publications

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“…However, this study did not control for the estrus cycle stage when the F2 mouse uterine tissue was collected for analysis. Indeed, the data presented indicate large variance in uterine weights in some of the groups (up to 3.7-fold variation; see Table 1 in [100]), consistent with the tissue being harvested at different estrus cycle stages. This study [100] was therefore excluded from further consideration.…”

Section: Resultssupporting

confidence: 61%

“…In this section we considered all studies that report changes in DNA methylation [56,60,100] and histone modification [57] in uteri of exposed animals. Hox genes are subject to epigenetic regulation [101,102]; therefore we also considered studies that report changes in Hox gene expression [54].…”

Section: Resultsmentioning

confidence: 99%

“…Two of those studies [65,66] are complementary to DNA methylation studies carried out by the same research groups ([56] and [60], respectively). In one study assessing trans-generational effects of BPA exposure, uterine histopathology and differential Hoxa10 DNA methylation were reported in adult offspring born to mice exposed to BPA neonatally (i.e., F2 generation mice) [100]. However, this study did not control for the estrus cycle stage when the F2 mouse uterine tissue was collected for analysis.…”

Section: Resultsmentioning

confidence: 99%

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Early programing of uterine tissue by bisphenol A: Critical evaluation of evidence from animal exposure studies

Suvorov

Waxman

2015

Reproductive Toxicology

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Exposure to Bisphenol A (BPA) during the critical window of uterine development has been proposed to program the uterus for increased disease susceptibility based on well-documented effects of the potent xenoestrogen diethylstilbestrol. To investigate this proposal, we reviewed 37 studies of prenatal and/or perinatal BPA exposure in animal models and evaluated evidence for: molecular signatures of early BPA exposure; the development of adverse uterine health effects; and epigenetic changes linked to long-term dysregulation of uterine gene expression and health effects. We found substantial evidence for adult uterine effects of early BPA exposure. In contrast, experimental support for epigenetic actions of early BPA exposure is very limited, and largely consists of effects on Hoxa gene DNA methylation. Critical knowledge gaps were identified, including the need to fully characterize short-term and long-term uterine gene responses, interactions with estrogens and other endogenous hormones, and any long-lasting epigenetic signatures that impact adult disease.

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Section: Resultssupporting

confidence: 61%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Early programing of uterine tissue by bisphenol A: Critical evaluation of evidence from animal exposure studies

Suvorov

Waxman

2015

Reproductive Toxicology

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“…In females, perinatal exposure to BPA increased the number of terminal end buds in mammary tissues of CD-1 mice exposed to estradiol later in life without affecting the terminal end buds in mammary tissues of C57BL/6 mice [22]. Furthermore, BPA increased the weight of offspring born to gestationally exposed ICR and adult CD1 Swiss mice, decreased the weight of offspring born to neonatally exposed ICR mice, but did not affect the weight of offspring born to gestationally and neonatally exposed C57BL/6J mice [15,[38][39][40]. Although timing of exposure may also play a role in birth weight following exposure to BPA, future studies should directly compare BPA effects in various strains to account for other potential confounders.…”

Section: Discussionmentioning

confidence: 93%

Mouse Strain Does Not Influence the Overall Effects of Bisphenol A-Induced Toxicity in Adult Antral Follicles1

Peretz

Neese

Flaws

2013

Biology of Reproduction

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Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) widely used in common consumer products containing polycarbonate plastics and epoxy resins. Previous studies indicate that other EDCs have species-dependent effects. Furthermore, some EDCs are known to have different effects in different strains within the same species. Little information, however, is known about whether the effects of BPA on the ovary differ by strain. Previous studies have shown that BPA inhibits follicle growth, induces atresia, and inhibits steroidogenesis and expression of steroidogenic enzymes in antral follicles from adult FVB mice. Thus, this study was designed to expand previous work by testing the hypothesis that mouse strain may differentially affect the susceptibility of adult antral follicles to BPA-induced toxicity. To test this hypothesis, antral follicles were mechanically isolated from adult FVB, CD-1, and C57BL/6 mice, individually cultured for 6-120 h and treated with either vehicle control (dimethylsulfoxide) or various concentrations of BPA (1.0 μg/ml, 10 μg/ml, or 100 μg/ml). After culture, media were subjected to measurements of hormone production via ELISA, and follicles were subjected to real-time PCR for analysis of genes known to regulate steroidogenesis, the cell cycle, and atresia. Overall, BPA inhibited follicle growth and steroidogenesis in all tested strains, but CD-1 follicles were slightly more sensitive to BPA at early time points than FVB and C57BL/6 follicles. These data suggest that CD-1, FVB, and C57BL/6 mice can all be used to investigate the effects of BPA on ovarian follicles.

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“…These structures expressed Hoxa10 (homeobox A10), a transcription factor that mediates proliferation of stromal tissue prior to implantation. Two other studies reported that BPA, at both low- and high doses, increased expression of Hoxa10 in prenatally exposed adult CD-1 and ICR mice (Bromer et al 2010; Hiyama et al 2011). …”

Section: Uterine Endometriummentioning

confidence: 96%

Bisphenol A and Reproductive Health: Update of Experimental and Human Evidence, 2007–2013

Peretz

Vrooman

Ricke

et al. 2014

Environ Health Perspect

467

301

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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.Citation: Peretz J, Vrooman L, Ricke WA, Hunt PA, Ehrlich S, Hauser R, Padmanabhan V, Taylor HS, Swan SH, VandeVoort CA, Flaws JA. 2014. Bisphenol A and reproductive health: update of experimental and human evidence, 2007–2013. Environ Health Perspect 122:775–786; http://dx.doi.org/10.1289/ehp.1307728

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Bisphenol-A (BPA) Affects Reproductive Formation across Generations in Mice

Cited by 29 publications

References 16 publications

Early programing of uterine tissue by bisphenol A: Critical evaluation of evidence from animal exposure studies

Early programing of uterine tissue by bisphenol A: Critical evaluation of evidence from animal exposure studies

Mouse Strain Does Not Influence the Overall Effects of Bisphenol A-Induced Toxicity in Adult Antral Follicles1

Bisphenol A and Reproductive Health: Update of Experimental and Human Evidence, 2007–2013

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