Integrated multi-omics profiling unveils a network of key signaling pathways governing ovarian function and systemic regulation in high-prolificacy goats

Abstract Background Prolificacy is a crucial economic trait in goat production, yet its underlying molecular mechanisms remain incompletely understood due to its polygenic nature. While previous studies have identified several candidate genes, a comprehensive understanding of the local and systemic regulatory networks is lacking. This study aims to dissect the complex molecular basis of high prolificacy in goats through an integrated multi-omics approach. Results We conducted transcriptomic, proteomic, and metabolomic profiling of ovarian tissues from high-fecundity (HF, n = 3) and low-fecundity (LF, n = 3) Chubao black-head goats, alongside multi-tissue (heart, liver, spleen, lung and kidney) transcriptome sequencing. Our analysis identified 1,075 differentially expressed genes (DEGs), 286 differentially expressed proteins (DEPs), and 55 differentially expressed metabolites (DEMs) in the ovary. Functional enrichment highlighted critical roles for signaling pathways such as Hippo, Wnt, MAPK, ECM-receptor interaction, and PI3K-Akt. Integrated cross-omics analysis revealed 10 genes (including CA3, CENPV, and GATM) consistently differentially expressed at both transcriptional and protein levels, and public single-cell RNA (scRNA) sequencing analysis further demonstrated their specific expression in key ovarian cell types including germ cells, granulosa cells, and theca cells. A core regulatory network centered on glycerophospholipid metabolism was constructed, showing coordinated dysregulation of metabolites like PC(20:3(5Z,8Z,11Z)/20:3(8Z,11Z,14Z)) and 1-Palmitoyl-sn-glycero-3-phosphocholine with genes PLA2G2C and PTDSS1. Multi-tissue transcriptomics further indicated that prolificacy involves both ovary-specific regulation and conserved systemic mechanisms. Conclusions This study demonstrates that high prolificacy in goats is a complex trait co-regulated by key local pathways in the ovary and systemic transcriptional adaptations. Our integrated multi-omics strategy provides a systematic molecular portrait of fecundity, identifying novel candidate genes and biomarkers with potential applications in genetic improvement programs for goats.