ESR1 Regulates Fecundity and Functions in Endometrial Stromal Cells of Sheep

Background: Endometrial stromal cells (ESCs) plasticity is critical for embryo survival and conceptus elongation; however, their genetic regulation remains unclear. Method: To elucidate the molecular mechanisms by which ESR1 regulates sheep fecundity through endometrial function, we investigated the effects of ESR1 on ovine ESCs in vitro. Results: Tissue distribution analysis revealed elevated ESR1 expression in the reproductive organs, particularly the endometrium, compared with that in non-reproductive tissues. Both ESR1 mRNA and its encoded ERα protein were significantly upregulated in the endometrium of high-fecundity Hu sheep compared to that in low-fecundity Hu sheep endometrium. Given the specific localisation of ERα in ESCs, we examined the functional roles of ESR1 in these cells in vitro. ESR1 knockdown in ESCs inhibited cell proliferation and induced apoptosis, concomitant with increased Caspase3 and Caspase9 mRNA expression. Furthermore, ESR1 interference triggered G0/G1 phase cell cycle arrest via upregulation of P53 and P21 and significantly impaired cell migration capacity. Collectively, these results demonstrate that ESR1 critically regulates ESCs proliferation, apoptosis, cell cycle progression, and migration. Conclusions: Our findings establish ESR1 as a key determinant of sheep fecundity and provide mechanistic insights into the high reproductive efficiency of Hu sheep.