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

Stem Cell Reports
Lauriane SèdesDavid H Volle

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.

Citations

Jul 2, 2019·Critical Reviews in Toxicology·Manoj Sonavane, Natalie R Gassman
Aug 14, 2019·Cellular and Molecular Life Sciences : CMLS·Manon GarciaDavid H Volle
Nov 21, 2018·International Journal of Molecular Sciences·Manon GarciaClaude Beaudoin
Oct 13, 2020·Frontiers in Endocrinology·Elikanah Olusayo AdegokeMyung-Geol Pang
Sep 4, 2020·Molecular Aspects of Medicine·M MonroseD H Volle
Aug 31, 2019·The Journal of Steroid Biochemistry and Molecular Biology·Hélène HolotaDavid H Volle
Apr 25, 2021·European Journal of Pediatrics·Sarah ZulkifliNoor Shafina Mohd Nor
Aug 23, 2020·Molecular and Cellular Endocrinology·Hélène HolotaDavid H Volle

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Datasets Mentioned

BETA
AB5535
GSE119012

Methods Mentioned

BETA
RNA-seq
PCR

Software Mentioned

Bowtie2
DESeq2
DESeq2 Bioconductor library
TopHat
HTSeq
Ensembl

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