卵丘细胞介导岩藻黄素通过NRF2信号减轻小鼠排卵后卵母细胞老化
Cumulus cells mediate the protective effect of the marine carotenoid fucoxanthin against postovulatory oocyte aging via NRF2 signaling
摘要
该预印本研究以超排ICR小鼠卵丘-卵母细胞复合体为对象,在体外老化12 h(纺锤体分析24 h)模型中比较岩藻黄素(1–10 µM)与虾青素,并用NRF2抑制剂ML385验证通路。5 µM岩藻黄素显著提高JC-1聚集/单体比值,改善线粒体膜电位与氧化还原状态;免疫荧光提示NRF2转位发生于卵丘细胞而非卵母细胞。原文结果部分截断,统计细节不全。
原文摘要
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 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.
推荐理由:首次将岩藻黄素抗排卵后老化作用定位到卵丘细胞的NRF2信号,而非卵母细胞,机制视角新颖;小鼠体外模型包含剂量、阳性对照和通路抑制剂验证,对ART中延长卵母细胞可用性有启发。但为预印本且结果与统计信息截断,需谨慎解读。
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