SIRT7-mediated H3K79 desuccinylation modulates functional activities of goat ovarian granulosa cells

Ovarian granulosa cells play essential roles in follicular development and reproductive aging; however, the epigenetic mechanisms that maintain their functional homeostasis remain incompletely understood. In this study, we explored the potential role of SIRT7-associated histone succinylation in goat ovarian granulosa cells by combining single-cell transcriptomic analysis with molecular and functional assays. Single-cell RNA sequencing revealed that SIRT7 was relatively enriched in granulosa cells and showed a decreasing trend during ovarian aging, accompanied by an overall increase in lysine succinylation. Functional analyses indicated that SIRT7 is associated with granulosa cell proliferation, viability, autophagy-related processes, and apoptosis. Further investigation showed that SIRT7 depletion was linked to increased succinylation at specific histone sites, among which histone H3 lysine 79 (H3K79) exhibited a relatively notable change. Using site-specific histone H3 mutants (H3K79E and H3K79R), we found that modifications at this site were associated with changes in cell cycle distribution, cell viability, and apoptosis in granulosa cells. Transcriptomic analysis further identified gene expression changes related to autophagy and apoptosis, with transmembrane protein 74 (TMEM74) emerging as a potential candidate. Functional experiments demonstrated that TMEM74 knockdown was associated with altered autophagy-related markers, reduced cell viability, and increased apoptosis. Collectively, these findings suggest a potential link among SIRT7 expression, H3K79-related regulation, TMEM74 expression, and autophagy in goat ovarian granulosa cells. This study provides new insights into the epigenetic regulation of ovarian function and aging, although the underlying mechanisms require further investigation.