Elsevier

Chemosphere

Volume 287, Part 3, January 2022, 132244
Chemosphere

Maternal exposure to bisphenol A induces fetal growth restriction via upregulating the expression of estrogen receptors.

https://doi.org/10.1016/j.chemosphere.2021.132244Get rights and content
Under a Creative Commons license
open access

Highlights

  • Human FGR placentae had increased BPA and estrogen levels and decreased BCRP levels.

  • BPA downregulated BCRP expression via ERs.

  • BCRP silencing promoted ER expression in BeWo cells.

  • ER inhibitor ICI-182780 reversed all the BPA-induced effects on BeWo cells.

Abstract

Bisphenol A (BPA) accumulation in the placenta leads to fetal growth restriction (FGR). Here we aimed to explore the effect and the underlying mechanism of BPA exposure on fetal development. ELISA was performed to measure estrogen levels in human placenta and BeWo cells. qRT-PCR and Western blotting were conducted to determine the expression of estrogen receptors (ERs), breast cancer resistance protein (BCRP), the key enzymes for ER synthesis, and DNA methyltransferases (DNMTs). Bisulfite-sequencing PCR analysis was performed to measure CpG methylation in ER genes. Flow cytometry was used to examine cell apoptosis. We found that human FGR placentae had significantly increased BPA and estrogen levels and decreased BCRP levels compared with healthy placentae. BPA downregulated BCRP expression via ERs, and BCRP silencing promoted ER expression in BeWo cells. Compared with vehicle treatment, BPA treatment significantly enhanced the expression of key enzymes for estrogen synthesis and ERs in BeWo cells. BPA treatment inhibited CpG methylation in ER genes, along with downregulated DNMT1 expression and upregulated DNMT3a and DNMT3b expression. BPA treatment significantly promoted BeWo cell apoptosis compared with vehicle treatment. Importantly, ER inhibitor ICI-182780 significantly reversed all the BPA-induced effects on BeWo cells. In conclusion, BPA promotes estrogen production and cell apoptosis in BeWo cells via upregulating ER expression, leading to FGR.

Keywords

Bisphenol A
Estrogen receptors
Trophoblast
DNA Methylation
Fetal growth restriction

Abbreviations

Bisphenol A
(BPA)
fetal growth restriction
(FGR)
estrogen receptors
(ERs)
breast cancer resistance protein
(BCRP)
DNA methyltransferases
(DNMTs)
ATP-binding cassette
(ABC)
abdominal circumference
(AC)
estimated fetal weight
(EFW)
umbilical artery
(UA)
pulsatility index
(PI)

Cited by (0)