Melatonin Ameliorates Stress-Induced Oocyte Developmental Impairment: Evidence from In Vivo and In Vitro Models

Stress compromises oocyte quality and reproductive performance, yet the comparative efficacy of MT and other antioxidants under stress remains unclear. This study compared MT and EGCG using an in vivo mouse restraint stress model and an in vitro porcine oocyte maturation model. In stressed mice, MT (0.1, 1, and 10 mg/kg) and EGCG (35, 65, and 100 mg/kg), administered via intraperitoneal (i.p.) injection every 12 h during the 48 h restraint period, improved oocyte developmental rates at appropriate doses, with MT showing superior efficacy at the optimal dose (1 mg/kg). Notably, MT, but not EGCG, reduced serum cortisol and CRH levels in stressed mice. In porcine oocytes, CRH supplementation during 48 h in vitro maturation (IVM) impaired oocyte maturation and embryo development, and MT dose-dependently rescued these defects, accompanied by reduced reactive oxygen species (ROS) accumulation and decreased cumulus cell apoptosis. RT-PCR analysis revealed that porcine oocytes and cumulus cells expressed MT1, but not MT2, transcripts. Collectively, evidence from two complementary models (mouse in vivo and porcine in vitro) supports MT as a promising supplement for oocyte protection under stress, through systemic and cellular mechanisms demonstrated in different species.