Multi-Tissue ceRNA Network Elucidates Exosome-Mediated Pathogenesis of Premature Ovarian Insufficiency with Implications for the Stem Cell Niche

Document Type : Original Article

Authors

1 Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

2 Department of Biology, Yazd University, Yazd, Iran

3 Hematology and Oncology Research Center, Non-communicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

4 Biotechnology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

5 Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran

Abstract

Premature Ovarian Insufficiency (POI) remains a significant cause of female infertility, yet its molecular mechanisms are incompletely understood. This study employed an integrative bioinformatics approach using multiple GEO datasets to construct a comprehensive ceRNA network across granulosa cells, cumulus cells, and exosomal miRNAs in POI. We identified distinct molecular signatures: granulosa cells showed cell cycle disruption, while cumulus cells exhibited differentiation pathway dysregulation. The core ceRNA network revealed 4 lncRNAs potentially regulating 31 mRNAs through sponging 4 key miRNAs (miR-423-5p, miR-106b-5p, miR-452-5p, and miR-3613-5p). Functional enrichment of these mRNAs implicated key stem cell-related pathways, including pluripotency and Hippo signaling. These findings provide novel insights into POI pathogenesis through exosome-mediated regulatory mechanisms, suggesting potential therapeutic targets for ovarian dysfunction and highlighting specific implications for the ovarian stem cell niche.

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Regenerative Biomedicine
Volume 1, Issue 4
December 2025
Pages 250-264

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