Cumulus cells mediate the protective effect of the marine carotenoid fucoxanthin against postovulatory oocyte aging via NRF2 signaling

Background Oocytes awaiting insemination undergo postovulatory aging, an oxidative stress-driven loss of developmental competence. Fucoxanthin (FX), the major carotenoid of the brown alga Undaria pinnatifida , acts through NRF2, which requires a nucleus and transcription; the metaphase-II oocyte has neither, so its site of action is unresolved. Purpose To determine whether FX delays postovulatory aging of mouse oocytes and identify the mediating compartment of the cumulus–oocyte complex. Study design Ex vivo study of intact cumulus–oocyte complexes from superovulated ICR mice aged for 12 h, or 24 h for spindle analysis. Astaxanthin (AX) served as benchmark and the NRF2 inhibitor ML385 tested pathway dependence. Methods Complexes were held in M16 medium with FX (1–10 µM) or AX (5 µM). Mitochondrial membrane potential, reactive oxygen species (ROS) and glutathione were measured with JC-1, DCFH-DA and monochlorobimane; spindle organization and cumulus-cell NRF2 localization by immunofluorescence. Results At the optimal 5 µM, FX raised the JC-1 aggregate-to-monomer ratio eight-fold over untreated aged oocytes (1.24 ± 0.10 versus 0.15 ± 0.02; p < 0.05), lowered ROS to 0.18 ± 0.04-fold and raised glutathione to 1.80 ± 0.02-fold of control (both p < 0.01), comparably to AX. ML385 abolished all three effects concentration-dependently. FX increased the cumulus-cell NRF2 nuclear-to-cytoplasmic ratio ( p < 0.05) and, after 24 h, nearly halved abnormal spindles ( p = 0.059). Conclusion FX preserves mitochondrial and redox status in postovulatory-aged oocytes through NRF2, which translocates in cumulus cells rather than the oocyte, identifying the cumulus cell as a target for extending oocyte usability in assisted reproduction.