Weight of the Evidence Evaluation of Low-Dose Reproductive and Developmental Effects of Bisphenol A

Gray, George M.; Cohen, Joshua T.; Cunha, Gerald R.; Hughes, Claude L.; McConnell, Ernest E.; Rhomberg, Lorenz R.; Sipes, I. G.; Mattison, Donald R.

doi:10.1080/10807030490513883

Cited by 87 publications

(57 citation statements)

References 73 publications

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“…Furthermore, a 2005 review of the BPA literature (43) shows that Ͼ90% of government-funded, low dose BPA studies report adverse health effects, supporting a reevaluation of human health risks associated with its exposure. This stands in stark contrast to a 2004 industry-sponsored review (44) concluding that the evidence supporting low dose effects of BPA is extremely weak. The results of our study strongly support the inclusion of epigenetic effects of xenobiotic chemicals like BPA into the risk assessment process, as well as the investigation of nutritional supplementation as a parental preventive approach to counteracting environmental influences on the epigenome.…”

Section: Discussioncontrasting

confidence: 40%

Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development

Dolinoy

Huang

Jirtle

2007

Proc. Natl. Acad. Sci. U.S.A.

1,217

890

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The hypothesis of fetal origins of adult disease posits that early developmental exposures involve epigenetic modifications, such as DNA methylation, that influence adult disease susceptibility. In utero or neonatal exposure to bisphenol A (BPA), a high-production-volume chemical used in the manufacture of polycarbonate plastic, is associated with higher body weight, increased breast and prostate cancer, and altered reproductive function. This study shows that maternal exposure to this endocrine-active compound shifted the coat color distribution of viable yellow agouti (A vy ) mouse offspring toward yellow by decreasing CpG (cytosineguanine dinucleotide) methylation in an intracisternal A particle retrotransposon upstream of the Agouti gene. CpG methylation also was decreased at another metastable locus, the CDK5 activator-binding protein (Cabp IAP ). DNA methylation at the A vy locus was similar in tissues from the three germ layers, providing evidence that epigenetic patterning during early stem cell development is sensitive to BPA exposure. Moreover, maternal dietary supplementation, with either methyl donors like folic acid or the phytoestrogen genistein, negated the DNA hypomethylating effect of BPA. Thus, we present compelling evidence that early developmental exposure to BPA can change offspring phenotype by stably altering the epigenome, an effect that can be counteracted by maternal dietary supplements.

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Section: Discussioncontrasting

confidence: 40%

Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development

Dolinoy

Huang

Jirtle

2007

Proc. Natl. Acad. Sci. U.S.A.

1,217

890

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“…There is controversial data about the safety of these products. Extensive safety research on BPA has shown that consumer products made with BPA are safe for their intended uses and pose no known risks to human health [10]. On the contrary, a large number of in vivo studies have reported adverse effects concerning low-dose exposures to BPA, even below the current reference dose [41].…”

Section: Introductionmentioning

confidence: 99%

Effect of prenatal exposure to bisphenol a on the vagina of albino rats: immunohistochemical and ultrastructural study

2014

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“…There is controversial data about the safety of these products. Extensive safety research on BPA has shown that consumer products made with BPA are safe for their intended uses and pose no known risks to human health (Haighton et al 2002, Gray et al 2004. On the contrary, a large number of in vivo studies have reported adverse effects concerning low-dose exposures to BPA, even below the current reference dose (Welshons et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Effect of prenatal exposure to the endocrine disruptor bisphenol A on mammary gland morphology and gene expression signature

Moral

Wang²,

Russo³

et al. 2007

Journal of Endocrinology

143

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Bisphenol A (BPA), known as an environmental endocrine disruptor, is widely used as a plasticizer. This study aims to investigate whether exposure in utero to BPA alters the architecture, proliferative index, and genomic signature of the rat mammary gland during critical stages of development. Pregnant rats were gavaged with 25 mg BPA/kg body weight (BW; low-dose group) or 250 mg BPA/kg BW (high-dose group) from day 10 post-conception to delivery. Female litters were euthanized at 21, 35, 50, and 100 days, and mammary glands were collected. Analysis of gland morphology was performed from whole-mounted mammary tissue, while proliferative index was determined by detection of bromodeoxyuridine incorporation in the epithelial cells. Genomic profiles were obtained by microarray analysis, and some genes were validated by real-time RT-PCR. BPA exposure induced changes in the mammary gland that were time and dose specific. High-dose exposure resulted in architectural modifications, mainly in the number of undifferentiated epithelial structures of the breast tissue. Proliferative index did not show remarkable differences by the effect of BPA. Low and high doses of BPA changed the gene expression signature of the mammary gland following a different fashion: low dose had the highest effect by 50 days, while high dose had a highest influence on gene expression by 100 days. Both doses presented a significant cluster of up-modulated genes related to the immune system at the age of maximal changes. Moreover, high-dose exposure induced changes in genes related to differentiation suggesting alterations in the normal development of the gland. The increase of undifferentiated structures and the changes in the gene expression profile at different ages suggest that prenatal exposure to BPA can affect the susceptibility of the mammary gland to transformation.

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Weight of the Evidence Evaluation of Low-Dose Reproductive and Developmental Effects of Bisphenol A

Cited by 87 publications

References 73 publications

Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development

Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development

Effect of prenatal exposure to bisphenol a on the vagina of albino rats: immunohistochemical and ultrastructural study

Effect of prenatal exposure to the endocrine disruptor bisphenol A on mammary gland morphology and gene expression signature

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