Integrative single-cell transcriptomics of sheep ovarian development reveals dynamic transcriptional programs relevant to reproductive traits

Sheep (<i>Ovis aries</i>) are valuable biomedical models for studying human reproductive biology, however, the transcriptional dynamics underlying their ovarian development remain insufficiently characterized. In this study, we profiled 61,649 single-cell transcriptomes from sheep ovarian tissues across key developmental stages: prenatal (E90), pre-puberty (M3), post-puberty (M6), and adulthood (Y2, Y4). We identified nine major cell types with distinct and dynamic gene expression patterns, highlighting significant developmental transitions. Notably, granulosa cells exhibited profound transcriptomic shifts, underscoring their critical role in oocyte maturation and follicular development. Key transcription factors, such as FOXO1 and ESR1, were identified as potential drivers of these transitions. Further cross-species comparisons revealed strong conservation in cell types, composition, and gene expression networks between sheep and human developing ovaries. Leveraging these conserved features, we uncovered context-dependent (e.g., cell-type-specific, developmental-stage-specific) associations with human reproductive traits and diseases. These findings advance our understanding of ovarian development in sheep and reinforce their utility as translational models in reproductive biology and disease research.