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4 December 2017 Low-dose bisphenol A activates the ERK signaling pathway and attenuates steroidogenic gene expression in human placental cells
Po-Wei Chu, Zhi-Jie Yang, Hui-Hsin Huang, Ai-An Chang, Yu-Chen Cheng, Gwo-Jang Wu, Hsin-Chieh Lan
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Abstract

Bisphenol A (BPA) is an industrial material used for many plastic products and is considered an endocrine disruptor. BPA can be released into the environment and can spread through the food chain. It is well known that BPA exposure leads to lesions, especially in the reproductive system. According to previous studies, BPA reduces newborn numbers in pregnant mice and affects placentation. The placenta is a special endocrine organ during pregnancy. It secretes important hormones, such as progesterone and estrogen, to maintain gestation. In steroid hormone synthesis, two specific enzymes are important: P450scc (CYP11A1) converts cholesterol to pregnenolone and aromatase (CYP19) induces androgen conversion to estrogen. To determine the effects of a low dose of BPA on hormone synthesis in the placenta, we used JEG-3 cells as a model. We found that the steroidogenic genes CYP11A1 and CYP19 were downregulated in human tissues by detectable concentrations of BPA (1–1000 nM), which do not affect cell viability. Furthermore, we demonstrated that BPA influenced the ERK signaling pathway and resulted in hormone reductions. An analysis of trophoblasts in primary culture from a term human placenta showed the same phenomena. Our data demonstrate that treatment with a low dose of BPA does not affect human placental cell survival, but decreases hormone production via to the downregulation of steroidogenic genes and ERK signaling pathway changes.

Summary Sentence

BPA inhibits steroidogenesis via ERK in placenta.

© The Author(s) 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Po-Wei Chu, Zhi-Jie Yang, Hui-Hsin Huang, Ai-An Chang, Yu-Chen Cheng, Gwo-Jang Wu, and Hsin-Chieh Lan "Low-dose bisphenol A activates the ERK signaling pathway and attenuates steroidogenic gene expression in human placental cells," Biology of Reproduction 98(2), 250-258, (4 December 2017). https://doi.org/10.1093/biolre/iox162
Received: 25 January 2017; Accepted: 30 November 2017; Published: 4 December 2017
JOURNAL ARTICLE
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KEYWORDS
bisphenol A (BPA)
ERK
progesterone
steroidogenesis
trophoblast
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