C-Phycocyanin ameliorates ovarian hyperstimulation syndrome by mitigating inflammation and enhances fertility in an OHSS mouse model

Ovarian hyperstimulation syndrome (OHSS) is a serious complication of assisted reproductive technology, particularly during gonadotropin-induced superovulation in in vitro fertilization and embryo transfer. Driven by elevated vascular endothelial growth factor (VEGF) levels and inflammation, OHSS increases vascular permeability and impairs reproductive capability. Given the lack of specific treatments, novel therapeutic strategies are urgently needed. C-Phycocyanin (PC), an extract from Spirulina, is known for its anti-inflammatory, antioxidant, anti-cancer, and immune-boosting properties. We established an OHSS mouse model and administered PC via gavage for 45 consecutive days to evaluate its effectiveness as a treatment for OHSS. Female mice were randomly divided into three groups: control, OHSS, and OHSS treated with PC. The protective effects of PC against OHSS were assessed at systemic, ovarian, and molecular levels. PC ameliorated the typical pathological features of OHSS in the murine model. Specifically, PC treatment significantly reduced body weight gain, ovarian weight, and vascular permeability, while restoring serum anti-Müllerian hormone and estradiol levels to near-normal ranges. PC restored aspartate aminotransferase and creatinine levels and decreased white blood cell count, and ovarian inflammation (Vegf, TNF-α, IL-6, IL-8 mRNA levels). Secondary and antral follicle counts, oocyte numbers, and polar body extrusion increased. Reactive oxygen species, mitochondrial aggregation, and apoptosis reduced; embryo development and litter size improved. No adverse offspring effects were observed. PC mitigates ovarian hyperstimulation syndrome by reducing VEGF-mediated vascular permeability and ovarian inflammation, improving ovarian reserve, oocyte quality, and reproductive outcomes in mice, supporting its potential clinical application.