Maternal aging can impair the quality and decrease the developmental competence of ovulated oocytes. In this study, compromised germinal vesicle breakdown (GVBD) was found in aged mice oocytes. Furthermore, we observed increased reactive oxygen species (ROS) and mitochondrial Ca²⁺ levels, along with reduced mitochondrial temperature in aged oocytes. Maternal aging also changed the crotonylation level in oocytes. Forkhead box O3 (FoxO3a), a member of the forkhead protein family involved in the regulation of cell survival and life span reached a peak level in the metaphase II stage. Compared with a younger group, FoxO3a expression increased in aged oocytes. Intracellular localization of FoxO3a changed from the cytoplasm to chromatin in response to aging. The expression of the upstream regulator nicotinamide-phosphoribosyltransferase (Nampt) peaked in the GVBD stage. Moreover, Nampt expression was increased in aged oocytes, and more intense staining of Nampt was found in aged mice ovary. To further study the role of Nampt in mitochondrial function, specific agonist P7C3 and inhibitor FK866 were applied to aged oocytes, and FK866 significantly decreased adenosine triphosphate and mitochondrial membrane potential. In conclusion, mitochondrial dysfunction in aged oocytes was associated with elevated FoxO3a, and suppression of Nampt could further impair mitochondrial function.

中文翻译：

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Nampt通过介导下游效应子FoxO3a影响衰老卵母细胞的线粒体功能

母体衰老会损害排卵卵母细胞的质量并降低其发育能力。在这项研究中，在老年小鼠卵母细胞中发现了受损的生发囊泡分解 (GVBD)。此外，我们观察到活性氧 (ROS) 和线粒体 Ca ^2+增加水平，以及衰老卵母细胞中线粒体温度的降低。母体衰老也改变了卵母细胞的巴豆酰化水平。叉头盒O3（FoxO3a）是叉头蛋白家族的一员，参与调节细胞存活和寿命，在II期达到峰值水平。与年轻组相比，FoxO3a 在老年卵母细胞中的表达增加。FoxO3a 的细胞内定位响应衰老而从细胞质变为染色质。上游调节剂烟酰胺-磷酸核糖基转移酶 (Nampt) 的表达在 GVBD 阶段达到峰值。此外，Nampt 在老年卵母细胞中的表达增加，并且在老年小鼠卵巢中发现了更强烈的 Nampt 染色。为了进一步研究 Nampt 在线粒体功能中的作用，将特异性激动剂 P7C3 和抑制剂 FK866 应用于衰老的卵母细胞，和 FK866 显着降低三磷酸腺苷和线粒体膜电位。总之，老年卵母细胞的线粒体功能障碍与 FoxO3a 升高有关，抑制 Nampt 可能进一步损害线粒体功能。