Spatial transcriptomics reveals the molecular dynamics of follicular development in the yak ovary under high-altitude hypoxia.

As a model organism exhibiting remarkable adaption to high-altitude conditions such as hypoxia and intense ultraviolet radiation, the yak offers valuable biological insights. A major unresolved question involves the regulatory mechanisms governing follicular development within a low-oxygen microenvironment. To address this, spatial transcriptomics were applied to characterize the spatial molecular architecture of the yak ovary and to delineate the dynamic follicular changes under high-altitude hypoxic conditions. A total of ten distinct ovarian cell populations were identified and the marker genes characteristic of each population were established. Furthermore, our findings indicate that follicular atresia is primarily associated with disruptions in cell-adhesion processes, whereas dysregulated lipid metabolism contributes to follicular lysis. Gene enrichment analyses across multiple stages of follicular development revealed significant enrichment in metabolic pathways, the HIF-1 signaling pathway, glutathione metabolism, and carbon-metabolism pathways. Dynamic molecular interactions involving MDH1/ENO1, MDH1/MDH2, ENO1/PKM and ENO1/HIF1A between oocytes and granulosa cells may constitute crucial regulatory mechanisms underlying follicular development under hypoxic conditions. Overall, this study provides a comprehensive molecular map of the yak ovary and identifies potential regulatory networks that governing follicular development, thereby offering fundamental molecular insights into the reproductive adaptation of yaks to high-altitude environments.