Cooperation of luteinizing hormone and estradiol in the promotion of goat oocyte maturation via regulation and activation of the GPR30 and EGFR signaling pathways

The luteinizing hormone (LH) is well established to trigger oocyte maturation and cumulus expansion in preovulatory follicles, primarily through activating the epidermal growth factor (EGF) signaling network. While previous studies have demonstrated that activation of the G protein-coupled estrogen receptor (GPR30) accelerates meiotic resumption and first polar body extrusion (FPE) in oocytes, the molecular mechanisms underlying GPR30 function in this process remain poorly defined. Here, cumulus-oocyte complexes (COCs) of goat follicles were used to investigate the interaction between the EGF network and GPR30 during oocyte maturation and ovulation. Our results showed that: LH signal was found to increase GPR30 protein levels via the EGF receptor signaling pathway (P < 0.05); Estradiol (E2) acts via GPR30 to promote ERK1/2 phosphorylation, cyclic adenosine monophosphate (cAMP) production, FPE, and the expression of cumulus expansion-related genes in COCs (P < 0.05), and E2 further enhances these functional outcomes by increasing epidermal growth factor receptor (EGFR) protein levels in cumulus cells. Collectively, these findings reveal a synergistic interaction between LH and E2 in regulating goat oocyte maturation: E2, via GPR30-mediated upregulation of EGFR, enhances COCs' responsiveness to LH-induced EGF signaling-thereby amplifying oocyte maturation efficiency and cumulus expansion. This study provides new insights into the integrated signaling network governing mammalian oocyte maturation and offers a potential molecular target for optimizing in vitro maturation protocols for goat.