Effects of Oral Exposure of Bisphenol A on mRNA Expression of Nuclear Receptors in Murine Placentae Assessed by DNA Microarray

Imanishi, Satoshi; Manabe, Noboru; Nishizawa, Hanako; Morita, Maki; Sugimoto, Miki; Iwahori, Mineko; Miyamoto, Hajime

doi:10.1262/jrd.49.329

Cited by 44 publications

(35 citation statements)

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“…The decrease in the number of fetuses in this study might have been caused by the direct effect of BPA on fetuses. In fact, microarray analysis has shown that BPA induces some nuclear receptor mRNAs after they bind to the estrogen receptor [10]. The effects of BPA on cytokine production should be examined at the protein level.…”

Section: Discussionmentioning

confidence: 99%

“…A lth ou gh DN A microarray has shown that the mRNAs of some nuclear receptors in the mouse placenta are increased by BPA administration [10], no detailed information is currently available about the effect of BPA on placentation and/or the fate of embryos and neonates. The present study shows the morphological changes in the pregnant uterus during placentation after BPA administration in mice.…”

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confidence: 99%

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Effects of Bisphenol A (BPA) on Placentation and Survival of the Neonates in Mice

et al. 2007

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Abstract. The effects of bisphenol A (BPA) on placentation have not been fully determined. The aim of this study was to clarify the structural changes of the placenta, abortion rate, and survival of neonates after BPA administration in mice. BPA (10 mg/kg/day) was administered to pregnant mice (BPA mice) subcutaneously from the first day of pregnancy (Day 0) to Day 7 (8 days total). The number of embryos and weights of whole uteri were measured on Days 10 and 12. Morphological changes in the placentae were examined by light microscopy on the corresponding days of pregnancy. The number of neonates was also counted. Survival rates were periodically calculated for neonates from the first day after parturition (P-Day 0) to P-Day 56. The number of embryos and weight of the uterus on Days 10 and 12 were significantly decreased by BPA injection. No notable differences were recognized between the left and right uteri. The proportion of the labyrinthine zone per whole placenta in the BPA mice became lower than that in the controls, and that of the metrial gland was higher in the BPA mice. The intervillous spaces of the placenta were narrower in the BPA mice. Degenerative changes were found in the trophoblastic giant cells and spongiotrophoblast layers of the BPA mice. The number of BPA mouse neonates was drastically decreased within 3 days after birth, and no mice survived after P-Day 56. The results suggest that BPA not only disrupts placental functions and leads to abortion through chronic stimulation of gene expression by binding to DNA but that it also affects the mortality of neonates through indirect exposure of embryos.

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Section: Discussionmentioning

confidence: 99%

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Effects of Bisphenol A (BPA) on Placentation and Survival of the Neonates in Mice

et al. 2007

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“…shown to activate at least nine nuclear receptors in murine placenta, including ERβ in the placenta of only male fetuses (36). BPA at 10 μM can significantly increase drug metabolism via stimulating the human orphan nuclear receptor-mediated transcription in HepG2 cells.…”

Section: Discussionmentioning

confidence: 99%

Effect of bisphenol A on drug efflux in BeWo, a human trophoblast-like cell line

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2005

Placenta

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. (2005) Effect of bisphenol A on drug efflux in BeWo, a human trophoblast-like cell line. Placenta, 26 Suppl.A, S96-S103. PMID: 15837075. Publisher's official version: http://dx.doi.org/10.1016/j.placenta. Keywords:Bisphenol A (BPA), P-glycoprotein (P-gp), BeWo cells, Drug efflux and 17β-estradiol (E2) Abstract:Bisphenol A (BPA) is a monomer of polycarbonate plastics that has estrogenic activities and has been shown to be a substrate for multidrug resistant efflux mechanisms, specifically, P-glycoprotein. Since the natural hormone estrogen reverses multidrug resistance in some cell types, we hypothesized that BPA might have a similar activity in trophoblasts. We have used BeWo cells as an in vitro model for human trophoblasts and calcein AM as a substrate for drug efflux mechanism to characterize BPA interactions with placental P-glycoprotein. We found that chronic exposure of BeWo cells to BPA did not alter intracellular calcein accumulation in a fashion that would be reflective of changes in Pglycoprotein expression. However, BeWo cells acutely exposed to BPA pre-treatment were observed to have a significantly decreased calcein accumulation suggesting a direct stimulatory effect on P-gp. Addition of cyclosporin A, a P-glycoprotein inhibitor and substrate, completely reversed BPA's effects on calcein accumulation and resulted in a net increase, relative to controls, in calcein accumulation by the BeWo cells. BPA was found not stimulate P-gp ATPase. Therefore, our results suggested that BPA stimulated drug efflux by BeWo cells probably by direct effects on P-glycoprotein.

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“…To d e t e r m i n e t h e e f f e c t s o f B P A ( W a k o P u r e Chemicals, Osaka, Japan), pregnant mice were orally administered with BPA (0.02, 2, 200, or 20,000 µg/kg/day; dissolved in olive oil. These doses were based on our previous studies [8,24,25]) in the afternoon (1200 to 1400) from 6.5 to 13.5 and from 6.5 t o 17.5 dpc (8 and 12 times, respectively). Vehicle controls were orally treated with purified olive oil (5 ml/kg) under the same conditions.…”

Section: Preparation Of Embryonic Tissuementioning

confidence: 99%

Effects of In Utero Exposure to Bisphenol A on mRNA Expression of Arylhydrocarbon and Retinoid Receptors in Murine Embryos

et al. 2005

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Abstract.To evaluate the effects of bisphenol A (BPA), a candidate endocrine disruptor (ED), on embryonic development, we examined the mRNA expression levels of the arylhydrocarbon receptor (AhR), which binds with many EDs and plays crucial roles in xenobiotic metabolism, and of the retinoic acid receptor (RAR) α and retinoid X receptor (RXR) α, key factors in nuclear receptordependent retinoid signal transduction, in murine embryos exposed in utero to BPA (0.02, 2, 200, and 20,000 µg/kg/day) at 6.5-13.5 or 6.5-17.5 days post coitum (dpc), using the real-time reverse transcription-polymerase chain reaction (RT-PCR) method. Extremely low-dose BPA (0.02 µg/kg/ day; 1/100 the dose of environmental exposure) remarkably increased AhR mRNA expression in the cerebra, cerebella, and gonads (testes and ovaries) of male and female 14.5-and 18.5-dpc-embryos. In utero exposure to BPA at 2, 200, and 20,000 µg/kg/day also increased levels of AhR mRNA. In gonads of 14.5-dpc-embryos, AhR mRNA levels were elevated and showed diphasic (U) dose-response curves following exposure to BPA, but inverted U dose-response curves were obtained for 18.5-dpcembryos. Exposure to BPA increased expression levels of RARα and RXRα mRNAs in the cerebra, cerebella, and gonads of male and female 14.5-and 18.5-dpc-embryos. Extremely low-dose BPA (0.02 µg/kg/day) increased RARα mRNA expression in the cerebella of male and female 14.5-and 18.5-dpc-embryos and in the gonads of female 14.5-dpc-embryos, and significantly increased RXRα mRNA expression in the cerebra and cerebella of male and female 14.5-dpc-embryos. The present findings confirm that in utero exposure to an extremely low dose of BPA up-regulates the mRNA expression of AhR, RARα, and RXRα in murine embryos and disrupts the receptor-dependent signal transducing systems, and will contribute to the assessment of the toxic effects of BPA on xenobiotic metabolism and retinoid signals in embryogenesis. Key words: Arylhydrocarbon receptor (AhR), Bisphenol A, Murine embryo, Retinoic acid receptor (RAR) α, Retinoid X receptor (RXR) α (J. Reprod. Dev. 51: [315][316][317][318][319][320][321][322][323][324] 2005) isphenol A [BPA; 2,2-bis (4-hydroxyphenyl) p r o p a n e ] , a c o m m o n p l a s t i c i z e r a n d a candidate environmental endocrine disruptor (ED), has toxicological effects on the reproductive, immunological, and nervous systems of mammals [1][2][3][4]. BPA binds to estrogen receptor-α (ERα; NR3A1) and -β (ERβ; NR3A2), and induces

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Effects of Oral Exposure of Bisphenol A on mRNA Expression of Nuclear Receptors in Murine Placentae Assessed by DNA Microarray

Cited by 44 publications

References 43 publications

Effects of Bisphenol A (BPA) on Placentation and Survival of the Neonates in Mice

Effects of Bisphenol A (BPA) on Placentation and Survival of the Neonates in Mice

Effect of bisphenol A on drug efflux in BeWo, a human trophoblast-like cell line

Effects of In Utero Exposure to Bisphenol A on mRNA Expression of Arylhydrocarbon and Retinoid Receptors in Murine Embryos

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