Hypermethylation of estrogen receptor promoter region in adult testis of rats exposed neonatally to bisphenol A

Doshi, Tanvi; Mehta, Suman; Dighe, Vikas; Balasinor, Nafisa; Vanage, Geeta

doi:10.1016/j.tox.2011.07.011

Cited by 157 publications

(93 citation statements)

References 49 publications

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“…Animal studies have shown that maternal exposure to drugs (10), stress (11), and endocrine disruptors (12) during pregnancy can alter epigenetic gene programming in the brain and contribute to neurodevelopmental deficits in offspring. Several studies have linked gestational (13,14) or neonatal (15,16) BPA exposure to long-lasting changes in DNA methylation and altered gene expression in nonneuronal tissues. Investigation of the epigenetic effects of BPA in the brain has been very limited (17,18) and has not explored whether environmentally relevant doses of BPA could induce enduring effects on the brain epigenome.…”

mentioning

confidence: 99%

Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure

Kundaković

Gudsnuk

Franks

et al. 2013

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

440

390

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Bisphenol A (BPA) is an estrogenic endocrine disruptor widely used in the production of plastics. Increasing evidence indicates that in utero BPA exposure affects sexual differentiation and behavior; however, the mechanisms underlying these effects are unknown. We hypothesized that BPA may disrupt epigenetic programming of gene expression in the brain. Here, we provide evidence that maternal exposure during pregnancy to environmentally relevant doses of BPA (2, 20, and 200 μg/kg/d) in mice induces sex-specific, dose-dependent (linear and curvilinear), and brain region-specific changes in expression of genes encoding estrogen receptors (ERs; ERα and ERβ) and estrogen-related receptor-γ in juvenile offspring. Concomitantly, BPA altered mRNA levels of epigenetic regulators DNA methyltransferase (DNMT) 1 and DNMT3A in the juvenile cortex and hypothalamus, paralleling changes in estrogen-related receptors. Importantly, changes in ERα and DNMT expression in the cortex (males) and hypothalamus (females) were associated with DNA methylation changes in the ERα gene. BPA exposure induced persistent, largely sex-specific effects on social and anxiety-like behavior, leading to disruption of sexually dimorphic behaviors. Although postnatal maternal care was altered in mothers treated with BPA during pregnancy, the effects of in utero BPA were not found to be mediated by maternal care. However, our data suggest that increased maternal care may partially attenuate the effects of in utero BPA on DNA methylation. Overall, we demonstrate that low-dose prenatal BPA exposure induces lasting epigenetic disruption in the brain that possibly underlie enduring effects of BPA on brain function and behavior, especially regarding sexually dimorphic phenotypes.environmental | fetal origin of adult disease

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mentioning

confidence: 99%

Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure

Kundaković

Gudsnuk

Franks

et al. 2013

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

440

390

View full text Add to dashboard Cite

show abstract

“…Fetal adrenal cortex development is dependent on placental estrogen and the existence of both types of estrogen receptors in the fetal gland (Kaludjerovic & Ward 2012) allows for a genomic action of BPA during developmental exposures. Additional nongenomic or epigenetic BPA actions in the adrenals, already reported for other tissues (Zsarnovszky et al 2005, Doshi et al 2011, cannot be excluded. The few reports on the effects of xenoestrogens in the adrenal cortex upon earlylife exposure support their effect on male steroidogenesis.…”

Section: Adrenal Histology and Functionmentioning

confidence: 84%

Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats

Panagiotidou¹,

Zerva²,

Mitsiou³

et al. 2013

Journal of Endocrinology

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Bisphenol A (BPA) is an estrogen-mimicking endocrine disruptor. Early-life exposures to low doses of BPA exert long-lasting effects on animals' reproductive and brain physiology. However, little is known about the effects of BPA on the stress-response system. Given the interaction of sex and stress hormones, we examined the effect of a low perinatal BPA exposure on the function of the hypothalamic-pituitary-adrenal (HPA) axis at rest and upon application of acute stress. Throughout pregnancy and lactation rats received daily 40 mg BPA/kg body weight orally via cornflakes. We studied the effect of this low but chronic exposure to BPA in the male and female offspring at puberty. BPA exposure led to abnormal adrenal histology including reduced zona reticularis especially in male offspring, hyperplasia of zona fasciculata in both sexes, and increased adrenal weight in female offspring. BPA-treated females had increased basal corticosterone and reduced hypothalamic glucocorticoid receptors (GR) levels. Stressed BPA-exposed females exhibited anxiety-like behavioral coping, a less rigorous corticosterone response, and did not downregulate GR in the hypothalamus, compared with control females. BPA-exposed males exhibited a heightened corticosterone stress response compared with females; they also displayed increased pro-opiomelanocortin mRNA levels and retained the prestress levels of pituitary corticotropin-releasing hormone-receptor 1, compared with control males. We found that perinatal chronic exposure to a low dose of BPA perturbs the basal and stress-induced activity of the HPA axis in a sexually dimorphic manner at adolescence. Exposure to BPA might contribute to increased susceptibility to stress-related disorders in later life.

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“…Foram encontrados estudos realizados em animais demonstrando os efeitos do plástico no organismo, relacionando-os com desordens dos sistemas cardiovascular 8 , endócrino [9][10][11][12] , reprodutor 13,14 , no metabolismo de vitaminas e sais minerais 15 , e ainda, na ação no código genético [16][17][18] . Os achados estão apresentados a seguir:…”

Section: Evidências Relacionadas a Desordens Na Saúde Dos Animaisunclassified

“…Três estudos investigaram os efeitos dos plásticos na genética [16][17][18] . Rochman et al 16 realizaram um estudo nos Estados Unidos (EUA).…”

Section: Ação No Código Genéticounclassified

Evidências em relação aos riscos à saúde pelo uso do plástico em embalagens alimentícias

et al. 2017

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Hypermethylation of estrogen receptor promoter region in adult testis of rats exposed neonatally to bisphenol A

Cited by 157 publications

References 49 publications

Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure

Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure

Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats

Evidências em relação aos riscos à saúde pelo uso do plástico em embalagens alimentícias

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