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

Moghimi-Moghadam, Seyedeh Mahdieh; Cheraghinik, Amirreza; Ahmadnia, Zahra; Hoseini, Seyed Mehdi; Montazeri, Fateme

doi:10.22034/jrb.2025.12.V1I4A1

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

Document Type : Original Article

Authors

Seyedeh Mahdieh Moghimi-Moghadam ¹^{, 2}

Amirreza Cheraghinik ¹

Zahra Ahmadnia ¹

Seyed Mehdi Hoseini ³^{, 4}

Fateme Montazeri ⁵

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

10.22034/jrb.2025.12.V1I4A1

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.

Keywords

Bioinformatics Analysis

ceRNA Network

Exosomal miRNAs

Premature Ovarian Insufficiency (POI)

Stem Cell Niche

Subjects