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BPA 与 FXRα 信号通路的串扰导致未分化生殖细胞稳态改变和男性生育障碍。

Crosstalk between BPA and FXRα Signaling Pathways Lead to Alterations of Undifferentiated Germ Cell Homeostasis and Male Fertility Disorders.

机构信息

INSERM U 1103, Université Clermont Auvergne, CNRS, UMR 6293, GReD, Laboratoire Génétique, Reproduction & Développement, 28 Place Henri-Dunant, 63000 Clermont-Ferrand, France.

Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France.

出版信息

Stem Cell Reports. 2018 Oct 9;11(4):944-958. doi: 10.1016/j.stemcr.2018.08.018. Epub 2018 Sep 20.

DOI:10.1016/j.stemcr.2018.08.018
PMID:30245210
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6178796/
Abstract

Several studies have reported an association between the farnesoid X receptor alpha (FXRα) and estrogenic signaling pathways. Fxrα could thus be involved in the reprotoxic effects of endocrine disruptors such as bisphenol-A (BPA). To test this hypothesis, mice were exposed to BPA and/or stigmasterol (S), an FXRα antagonist. Following the exposure to both molecules, wild-type animals showed impaired fertility and lower sperm cell production associated with the alteration of the establishment and maintenance of the undifferentiated germ cell pool. The crosstalk between BPA and FXRα is further supported by the lower impact of BPA in mice genetically ablated for Fxrα and the fact that BPA counteracted the effects of FXRα agonists. These effects might result from the downregulation of Fxrα expression following BPA exposure. BPA and S act additively in human testis. Our data demonstrate that FXRα activity modulates the impact of BPA on male gonads and on undifferentiated germ cell population.

摘要

几项研究报告称，法尼醇 X 受体α（FXRα）与雌激素信号通路之间存在关联。因此，Fxrα 可能参与了双酚 A（BPA）等内分泌干扰物的生殖毒性作用。为了验证这一假设，研究人员用 BPA 和/或stigmasterol（S），一种 FXRα 拮抗剂，对小鼠进行了暴露处理。在接触这两种分子后，野生型动物表现出生育能力受损和精子细胞生成减少，这与未分化的生殖细胞库的建立和维持的改变有关。BPA 与 FXRα 之间的相互作用进一步得到了支持，因为在 Fxrα 基因缺失的小鼠中，BPA 的影响较小，而且 BPA 抵消了 FXRα 激动剂的作用。这些影响可能是由于 BPA 暴露后 Fxrα 表达下调所致。BPA 和 S 在人类睾丸中具有相加作用。我们的数据表明，FXRα 活性调节了 BPA 对男性性腺和未分化生殖细胞群体的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/ca5c6c4e09dc/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/6d187d4fc910/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/36e8934a1f07/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/a5eabef07830/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/14e4a77a9159/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/99cf1f33e32f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/3df599972b06/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/ca5c6c4e09dc/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/6d187d4fc910/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/36e8934a1f07/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/a5eabef07830/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/14e4a77a9159/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/99cf1f33e32f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/3df599972b06/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/748a/6178796/ca5c6c4e09dc/gr7.jpg

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