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bioRxiv · 10.64898/2026.11.01.763385

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

Oh, C.·Kwon, S.-T.·Kwon, H. N.·Woo, J.-H.·Lee, J. E.·Jung, S.
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Abstract

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 {micro}M) or AX (5 {micro}M). 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 {micro}M, 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.

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Oh, C., Kwon, S.-T., Kwon, H. N., Woo, J.-H., Lee, J. E., Jung, S.. 2026-11-02. Cumulus cells mediate the protective effect of the marine carotenoid fucoxanthin against postovulatory oocyte aging via NRF2 signaling. https://doi.org/10.64898/2026.11.01.763385

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