ArticleJournal of ovarian research2025
Intrinsic differences in mTOR activity mediates lineage-specific responses to cyclophosphamide in mouse and human granulosa cells.
Article in Journal of ovarian research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Effect of estradiol on in vitro maturation of immature oocytes in cyclophosphamide-induced premature ovarian failure in NMRI mice: An experimental study.International journal of reproductive biomedicine · 2025Article
- Identify the therapeutic role and potential mechanism of α-cyperone in diminished ovarian reserve based on network pharmacology, molecular docking, Lip-MS and experimental validation.Frontiers in pharmacology · 2025Article
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Authors and funding
11 authors.
Funding
Abstract
backgroundCyclophosphamide (CTX) often induces oocyte and granulosa cell injury, leading to fertility loss in young female cancer survivors. Deciphering the mechanisms underlying follicular cell injury could offer novel insights into fertility preservation. Granulosa cells represent the most abundant cell type within the follicles and can be generally categorized as cumulus granulosa cells (CGCs) and mural granulosa cells (MGCs). Despite the essential roles of granulosa cells in supporting ovarian function in physiological conditions, their distinct lineage-specific responses to CTX remains elusive.
resultsHere, we performed a genome-wide transcriptome analysis of murine mural and cumulus granulosa cells before and after CTX administration. Compared with MGCs, CGCs exhibited higher basal mammalian target of rapamycin (mTOR) activity and an increased DNA damage response post-injury. Pharmacological mTOR suppression or RNA interference-mediated gene silencing of Raptor, a key component of the mTORC1 complex, significantly reduced DNA damage in granulosa cells induced by 4-HC, an activated form of CTX. Notably, by examining human granulosa cells in response to 4-HC, our results uncovered a conserved role of mTOR inhibition in ovarian protection.
conclusionsTaken together, our findings reveal that intrinsic variations in mTOR activity in CGC and MGC lineages determine their differential responses to CTX. Targeting this signaling pathway may prove beneficial in mitigating CTX-induced granulosa cell apoptosis and protecting against ovarian injury.
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