The EZH2-H3K27me3 axis modulates aberrant transcription and apoptosis in cyclophosphamide-induced ovarian granulosa cell injury.

ABSTRACT: Chemotherapy-induced ovarian damage and infertility are significant concerns for women of childbearing age with cancer; however, the underlying mechanisms are still not fully understood. Our study has revealed a close association between epigenetic regulation and cyclophosphamide (CTX)-induced ovarian damage. Specifically, CTX and its active metabolite 4-hydroperoxy cyclophosphamide (4-HC) were found to increase the apoptosis of granulosa cells (GCs) by reducing EZH2 and H3K27me3 levels, both in vivo and in vitro. Furthermore, RNA-seq and CUT&Tag analyses revealed that the loss of H3K27me3 peaks on promoters led to the overactivation of genes associated with transcriptional regulation and apoptosis, indicating that stable H3K27me3 status could help to provide a safeguard against CTX-induce

SUBMITTER: Chen Y 

PROVIDER: S-EPMC10646043 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature