IGF-1 supplementation improves in vitro maturation quality of Capra hircus oocytes via PDE3A activation, gap junction remodeling, apoptosis suppression, and kisspeptin signaling

Introduction – Although follicular development and oocyte competence depend on insulin-like growth factor-1 (IGF-1), its optimal dose and molecular mechanisms during goat in vitro maturation (IVM) remain unclear. Methods – Cumulus-oocyte complexes from Capra hircus were cultured for 22 h in IVM media containing 0, 50, 100, or 150 ng/mL IGF-1, and nuclear maturation was assessed by first polar body extrusion. To elucidate mechanisms, Gja4 and PDE3A mRNA, IL-6, caspase-3, and caspase-9 mRNA were measured by qPCR, kisspeptin protein was quantified by ELISA, and correlation and structural path analyses were performed. Results – IGF-1 at 100 ng/mL significantly increased maturation rate compared with control, whereas 150 ng/mL provided no additional benefit, indicating a biphasic response. At 100 ng/mL, PDE3A expression and kisspeptin protein levels increased, while Gja4 and caspase-3 expression decreased; IL-6 and caspase-9 remained unchanged. Correlation and structural path analyses identified PDE3A-mediated meiotic restart and suppression of caspase-3-dependent apoptosis as primary drivers of improved maturation. Discussion – Optimized IGF-1 supplementation enhances goat oocyte quality through coordinated regulation of meiotic activation, gap junction remodeling, and apoptosis inhibition. These findings may improve the efficiency of goat in vitro embryo production and support Sustainable Development Goal 2 (Zero Hunger) by strengthening reproductive efficiency and livestock productivity.

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