Genome-wide association study reveals candidate genes for litter size and function validation of MMP16 gene in lop sheep

As a premium indigenous sheep breed endemic to Tarim Basin, Xinjiang, China, Lop sheep demonstrate remarkable adaptability to extreme arid, high-temperature and sandstorm-prone environments, with some ewes exhibiting exceptional prolificacy. To elucidate the genetic regulation of this reproductive trait, we integrated whole-genome resequencing and transcriptome sequencing, conducting genome-wide association study on 110 Lop ewes with particular emphasis on the regulatory role in litter size determination of <i>MMP16</i> gene. Through multi-dimensional investigations including qRT-PCR, immunohistochemistry, ovarian granulosa cells culture, and transcriptome sequencing, we revealed that <i>MMP16</i> gene significantly influences folliculogenesis and ovulation by modulating extracellular matrix (ECM) remodeling and PI3K-AKT signaling pathway activation. Our research systematically elucidates genetic variations associated with prolificacy in Lop sheep and deciphers the biological function of <i>MMP16</i> gene, providing novel insights into the genetic architecture of ovine reproductive traits. The findings establish a theoretical foundation for molecular marker-assisted breeding and the exploitation of superior germplasm resources.