The epithelial Na + channel (ENaC) in ovarian granulosa cells modulates Ca 2+ mobilization and gonadotrophin signaling for estrogen homeostasis and female fertility.

Autor: Ma X; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China., Xu R; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China., Chen J; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China.; Jinan University, Guangzhou, China., Wang S; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China., Hu P; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China., Wu Y; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China., Que Y; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China., Du W; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China., Cai X; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China., Chen H; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China., Guo J; School of Medicine, The Chinese University of Hong Kong, Shenzhen, China., Li TC; Department of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China., Ruan YC; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China. sharon.yc.ruan@polyu.edu.hk.; Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen, China. sharon.yc.ruan@polyu.edu.hk.
Jazyk: angličtina
Zdroj: Cell communication and signaling : CCS [Cell Commun Signal] 2024 Aug 14; Vol. 22 (1), pp. 398. Date of Electronic Publication: 2024 Aug 14.
DOI: 10.1186/s12964-024-01778-5
Abstrakt: Ovarian granulosa cells are essential to gonadotrophin-regulated estrogen production, female cycle maintenance and fertility. The epithelial Na + channel (ENaC) is associated with female fertility; however, whether and how it plays a role in ovarian cell function(s) remained unexplored. Here, we report patch-clamp and Na + imaging detection of ENaC expression and channel activity in both human and mouse ovarian granulosa cells, which are promoted by pituitary gonadotrophins, follicle stimulating hormone (FSH) or luteinizing hormone (LH). Cre-recombinase- and CRISPR-Cas9-based granulosa-specific knockout of ENaC α subunit (Scnn1a) in mice resulted in failed estrogen elevation at early estrus, reduced number of corpus luteum, abnormally extended estrus phase, reduced litter size and subfertility in adult female mice. Further analysis using technologies including RNA sequencing and Ca 2+ imaging revealed that pharmacological inhibition, shRNA-based knockdown or the knockout of ENaC diminished spontaneous or stimulated Ca 2+ oscillations, lowered the capacity of intracellular Ca 2+ stores and impaired FSH/LH-stimulated transcriptome changes for estrogen production in mouse and/or human granulosa cells. Together, these results have revealed a previously undefined role of ENaC in modulating gonadotrophin signaling in granulosa cells for estrogen homeostasis and thus female fertility.
(© 2024. The Author(s).)
Databáze: MEDLINE
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