Unveiling the formation of the primordial follicle pool in goats: insights from single-cell omics analysis.

In brief: In brief The establishment of the primordial follicle pool governs female reproductive lifespan but is poorly understood in ruminants. This study provides the first single-cell atlas of goat ovarian development, revealing key cellular interactions and identifying LUZP2 as a candidate oocyte-associated regulator potentially involved in primordial follicle formation. Abstract: Mammalian primordial follicles, essential for female reproduction, form a finite nonrenewable pool perinatally, with species-specific developmental variations. This study employed single-cell RNA sequencing to map the transcriptional landscape of primordial follicle formation in goats, focusing on fetal (embryonic day 75 [E75], E140) and postnatal (postpartum day 0) stages using over 37,000 ovarian cells. These stages encompassed the midfetal stage (after syncytial rupture and the beginning of primordial follicle formation) to the formation of the primordial follicle pool in goats. Seven ovarian cell types were identified, with oocyte and granulosa cell subtypes analyzed in depth. Key interactions between oocytes, proliferative granulosa cells, and granulosa cells-1 via tight junctions, ECM-receptor signaling, and endocytosis were implicated in primordial follicle assembly. Transcription factor analysis identified LUZP2 as a novel oocyte-enriched transcriptional regulator potentially involved in primordial follicle formation, and its expression pattern was validated by real-time quantitative PCR and immunofluorescence. Overall, this study provides the first single-cell transcriptomic atlas of goat ovarian development, delineating dynamic gene expression patterns and cellular interactions during primordial follicle pool establishment. These findings advance understanding of conserved and species-specific mechanisms governing female reproductive lifespan in mammals.