Dynamic Remodeling of Oocyte‐Granulosa Cell Communication During Bovine Folliculogenesis Revealed by Transcriptomic Meta‐Analyses

Abstract

Ovarian folliculogenesis relies on tightly coordinated communication between the oocyte and surrounding granulosa cells, yet how this molecular dialogue is remodeled during follicle development remains poorly understood. Here, we reconstructed stage‐specific ligand–receptor communication networks through a transcriptomic meta‐analysis integrating bovine secondary, early antral, and middle antral follicles. Our analyses revealed that oocyte–granulosa cell communication undergoes progressive remodeling during folliculogenesis, with distinct signaling programs characterizing successive developmental stages. Secondary follicles were predominantly associated with extracellular matrix organization, cell adhesion, and early metabolic regulation. During the early antral stage, signaling shifted toward lipid, steroid, and vitamin metabolism, identifying this phase as a major metabolic transition. Middle antral follicles exhibited a marked increase in communication complexity, with enrichment of PI3K–AKT, mTOR, RAS, Hippo, and cell adhesion pathways accompanying the acquisition of developmental competence. Additional analyses of Brilliant Cresyl Blue‐classified cumulus–oocyte complexes identified competence‐associated ligand‐receptor interactions, while independent validation using the EmbryoGENE dataset confirmed stage‐specific expression patterns and highlighted CD47, FGF21, and GPC6 as candidate regulators of oocyte developmental competence. This study provides a comprehensive transcriptomic framework describing the dynamic remodeling of oocyte–granulosa cell communication during bovine folliculogenesis. Beyond confirming established signaling pathways, it identifies novel candidate interactions and offers a biologically grounded resource to guide future functional studies and the optimization of in vitro follicle and cumulus–oocyte complex culture systems.