miR-149 Promotes Apoptosis of Ovarian Granulosa Cells Through Inducing Caspase 8 Expression

Follicular atresia constitutes a major constraint on sow reproductive performance. Aberrant miRNA expression is well documented to promote follicular atresia. However, precise identification of the functional miRNAs responsible for this process remains a formidable challenge. In this study, we integrated multiple transcriptome datasets and identified miR-149, a miRNA located within the quantitative trait loci (QTL) associated with litter size in sow. Notably, miR-149 was highly expressed in atretic follicles and ovaries of sow with low litter size. Subsequent in vitro culture of ovarian granulosa cells (GCs) combined with miR-149 overexpression assays revealed that miR-149 significantly promotes the expression of cleaved caspase 3 (c-caspase 3), a marker of apoptosis in ovarian GCs. Mechanistic studies revealed that miR-149 functions as small activating RNA (saRNA) to activate the transcription of Caspase 8. This triggers the death receptor-mediated apoptotic, upregulates the expression of Caspase 3, and ultimately accelerates apoptosis in ovarian GCs. Collectively, these results indicate that miR-149 acts as negative regulator of sow reproduction. This study elucidates the miR-149/Caspase 8/Caspase 3 signaling axis as a novel pathway governing sow fertility, which provides molecular targets for improving reproductive performance in sow.