PI3K-AKT signaling pathway mediates placental cotyledon development and angiogenesis in goats†

Placental cotyledons play a crucial role in material exchange and gas transportation between the ruminant mother and fetus and their proper development is essential for the intrauterine growth and development of the fetus. This study aimed to investigate the relationships between cotyledon size, litter size, and birth weight, while also identifying the key candidate genes involved in cotyledon development. Based on 95 postpartum goat placentas, significant positive associations were observed between cotyledon area, litter size, and birth litter weight. Histological examination showed a significant increase in capillary density with increasing cotyledon area, accompanied by significant changes in the cotyledon villus structure. Through the RNA-seq analysis of large (diameter > 30 mm), medium (diameter between 10-30 mm), and small (diameter < 10 mm) placental cotyledons, a total of 1103 differentially expressed genes (DEGs) were identified while RT-qPCR experiments confirmed the reliability of the sequencing results. The KEGG analysis indicated that the identified DEGs were primarily enriched in pathways such as the PI3K-AKT signaling pathway, the ECM-receptor interaction, the JAK-STAT signaling pathway, and the Estrogen signaling pathway. In conjunction with Gene Ontology functional annotations and Gene Set Enrichment Analysis (GSEA), the Spp1, Efna3, Igta3, and Csf1r genes were identified as potential candidate genes affecting the development and angiogenesis of goat placental cotyledons. These findings provide important insights into the mechanisms underlying the development of goat cotyledons and their relationship with the reproductive performance of goats.