Astaxanthin and omega-3 fatty acids enhance endometrial receptivity in a rat model of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) adversely affects endometrial receptivity and fertility outcomes. This study investigated whether combining high-dose antioxidants (astaxanthin or omega-3 fatty acids) with metformin improves endometrial receptivity markers, reduces oxidative stress, and normalizes hormone profiles in a PCOS rat model compared to metformin alone or no treatment. Fifty-six female Sprague–Dawley rats (200-250g) were divided into seven groups: Control, PCOS, PCOS + Met, and groups receiving metformin plus either astaxanthin (PCOS + Met + AX5 or PCOS + Met + AX10) or omega-3 (PCOS + Met + OMG400 or PCOS + Met + OMG1000). PCOS was induced using letrozole for 21 days, followed by one week of treatment. After establishing endometrial receptivity, uterine tissues were analyzed histopathologically, immunohistochemically, and biochemically on day 5. The PCOS group demonstrated significant increases in body weight and oxidative stress markers (malondialdehyde) compared to controls (p < 0.001). High-dose antioxidant supplementation (PCOS + Met + AX10 and PCOS + Met + OMG1000) significantly improved these parameters (p < 0.001). Immunohistochemically, integrin β3 expression increased while mucin 1 (MUC-1) decreased in high-dose groups compared to PCOS (p < 0.001). The LH:FSH ratio normalized to control levels in PCOS + Met + AX10 and PCOS + Met + OMG1000 groups. Histological examination revealed enhanced endometrial morphology and increased pinopode-like structure formation in antioxidant-supplemented groups. High-dose astaxanthin and omega-3 fatty acid supplementation, combined with metformin, may enhance endometrial receptivity in PCOS by reducing oxidative stress and modulating key implantation markers. This therapeutic approach could potentially improve fertility outcomes in women with PCOS. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.