SERPINE2 Promotes Proliferation of Granulosa Cells With FecB Mutation in Small‐Tailed Han Sheep by Regulating TERT

During follicular development, ovarian granulosa cells (GCs) proliferate to support follicle growth and endocrine function. Telomerase reverse transcriptase (TERT) contributes to telomere maintenance and is associated with the proliferative capacity of GCs. In this study, we investigated whether serine protease inhibitor E2 (SERPINE2) regulates GC function in Small-tailed Han sheep with different FecB genotypes through modulation of TERT expression. Primary GCs were isolated from ewe ovaries, genotyped for FecB, and cultured in vitro. SERPINE2 and TERT expression were evaluated by RT-qPCR and Western blotting. SERPINE2 was overexpressed or knocked down in primary GCs, followed by assessment of relative telomere length, cell proliferation (EdU and CCK-8 assays and cell-cycle marker expression), ovulation-related gene expression, and estradiol secretion (ELISA). SERPINE2 expression and relative telomere length were significantly higher in FecB BB GCs than in FecB ++ GCs. Overexpression of SERPINE2 upregulated TERT expression, increased relative telomere length, promoted the proliferation of GCs, and enhanced the expression of ovulation-related genes (PGR, ESR1) and estradiol secretion. Conversely, inhibition of SERPINE2 produced opposite effects. These findings suggest that SERPINE2 promotes the proliferation of GCs and regulates ovulation-related gene expression and hormone secretion in FecB mutant sheep by modulating TERT expression, providing new insights into the molecular mechanisms underlying sheep reproductive performance.