Genome-Wide Analysis of DNA Methylation Profiles on Jining Grey Goat Uterus Associated with Prolificacy Using Whole-Genome Bisulfite Sequencing

Litter size is a vital economic trait in goat production, and previous studies on its regulatory mechanisms mainly focus on ovarian tissues. The genome-wide DNA methylation landscape of the goat uterus and its association with prolificacy remain poorly understood. In this study, we performed whole-genome bisulfite sequencing (WGBS) on uterine tissues from high-prolificacy (HP) and low-prolificacy (LP) Jining Grey Goats to explore epigenetic regulatory mechanisms underlying litter size. A total of 880 differentially methylated regions (DMRs) and 274 differentially methylated genes (DMGs) were identified. Combined with transcriptome data, 21 genes were found to exhibit both differential methylation and differential expression. Three candidate genes (CFAP43, PLPPR1 and TRPC3) and their corresponding DMRs were further verified via bisulfite sequencing PCR (BSP). Integrated analysis highlighted CFAP43, TTC21A, and CROCC as key candidate genes functionally associated with ciliary structure and maintenance, whose methylation and expression patterns correlate with the litter size phenotype. This study establishes the first genome-wide DNA methylation map of the Jining Grey Goat uterus. We demonstrate that DNA methylation modulates the expression of CFAP43, TTC21A and CROCC, and further regulates uterine ciliary function to affect goat prolificacy. Our findings provide novel epigenetic insights into goat reproductive traits and supply candidate molecular markers for goat breeding.