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ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Reproduction
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1593595
RGS14 Binds to GNAI3 and Regulates the Proliferation and Apoptosis of Human Spermatogonial Stem Cells by Affecting PLPP2 Expression and MAPK Signaling
Provisionally accepted- 1Changsha Hospital for Maternal and Child Health Care, Changsha, China
- 2Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan Province, China
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Non-obstructive azoospermia (NOA) is a severe form of male infertility characterized by the absence of sperm in the ejaculate due to impaired spermatogenesis. Spermatogonial stem cells (SSCs) play a crucial role in maintaining male fertility by ensuring continuous sperm production. However, the molecular mechanisms regulating SSC fate and their involvement in NOA remain largely unknown. In this study, singlecell RNA sequencing was utilized to analyze gene expression profiles in normal and NOA testes, revealing a significant downregulation of RGS14 in SSCs of NOA patients.It was found that RGS14 interacts with GNAI3 and modulates SSC proliferation and apoptosis by regulating the expression of PLPP2 and the MAPK signaling pathway.Knockdown of RGS14 significantly inhibited SSC proliferation and increased apoptosis, effects that were partially rescued by overexpression of PLPP2. Additionally, both PLPP2 and GNAI3 were found to be significantly downregulated in NOA patients, correlating with the expression pattern of RGS14. These findings provide novel insights into the molecular mechanisms underlying SSC dysfunction in NOA. The dysregulation of RGS14, GNAI3, and PLPP2 may contribute to the pathogenesis of NOA, elucidating the role of RGS14 in SSC fate determination and identifying potential therapeutic targets for male infertility.
Keywords: RGS14, GNAI3, PLPP2, spermatogonial stem cells, NOA, proliferation
Received: 14 Mar 2025; Accepted: 09 Apr 2025.
Copyright: © 2025 Liu, Deng, Liu, Peng, Liu, Chen, Fang, Zhang and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dai Zhou, Changsha Hospital for Maternal and Child Health Care, Changsha, China
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