<br>FOXM1 通过调节衰老卵母细胞中的 p21 来影响氧化应激、线粒体功能和 DNA 损伤反应,Theriogenology

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FOXM1 通过调节衰老卵母细胞中的 p21 来影响氧化应激、线粒体功能和 DNA 损伤反应
Theriogenology ( IF 2.4 ) Pub Date : 2024-08-10 , DOI: 10.1016/j.theriogenology.2024.08.010
Wenjie Yu ₁ , Xiaoshi Cai ₁ , Chen Wang ₁ , Xinyue Peng ₁ , Lingxia Xu ₁ , Yan Gao ₁ , Tian Tian ₂ , Guangying Zhu ₃ , Yuan Pan ₄ , Hongzhong Chu ₅ , Shuang Liang ₁ , Chengzhen Chen ₁ , Nam-Hyung Kim ₆ , Bao Yuan ₁ , Jiabao Zhang ₁ , Hao Jiang ₁

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排卵后衰老卵母细胞的受精能力和胚胎存活率降低，导致雌性动物的繁殖率降低。然而，卵母细胞排卵后衰老过程中涉及的关键调控基因和相关调控机制仍不清楚。在这项研究中，RNA-Seq 揭示了 3237 个基因在 MII 和衰老期（MII + 24 h）之间在猪卵母细胞中差异表达。FOXM1 的表达水平在衰老阶段升高，在猪卵母细胞衰老过程中，还观察到 FOXM1 在许多关键生物过程中富集，例如细胞衰老、对氧化应激的反应和转录。既往研究表明，FOXM1 参与氧化应激、DNA 损伤修复、线粒体功能和细胞衰老等多种生物过程的调节，这表明 FOXM1 可能在排卵后衰老过程中发挥关键作用。因此，在这项研究中，我们研究了 FOXM1 对卵母细胞衰老过程中氧化应激、线粒体功能、DNA 损伤和细胞凋亡的影响和机制。我们的研究表明，与 MII 阶段的卵母细胞相比，衰老卵母细胞表现出 ROS 水平显着增加，GSH 、 SOD 、 T-AOC 和 CAT 水平显著降低，并且 FOXM1 抑制加剧了衰老卵母细胞中这些水平的变化。此外，FOXM1 抑制增加了衰老卵母细胞中 DNA 损伤、细胞凋亡和细胞衰老的水平。p21 抑制剂减轻了 FOXM1 抑制对氧化应激、线粒体功能和 DNA 损伤的影响，从而减轻了衰老卵母细胞的衰老程度。这些结果表明，FOXM1 在猪卵母细胞衰老中起着至关重要的作用。本研究有助于理解 FOXM1 在猪卵母细胞衰老过程中的功能和机制，为防止卵母细胞衰老和优化卵母细胞体外培养条件提供理论依据。

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FOXM1 affects oxidative stress, mitochondrial function, and the DNA damage response by regulating p21 in aging oocytes

Fertilization capacity and embryo survival rate are decreased in postovulatory aging oocytes, which results in a reduced reproductive rate in female animals. However, the key regulatory genes and related regulatory mechanisms involved in the process of postovulatory aging in oocytes remain unclear. In this study, RNA-Seq revealed that 3237 genes were differentially expressed in porcine oocytes between the MII and aging stages (MII + 24 h). The expression level of FOXM1 was increased at the aging stage, and FOXM1 was also observed to be enriched in many key biological processes, such as cell senescence, response to oxidative stress, and transcription, during porcine oocyte aging. Previous studies have shown that FOXM1 is involved in the regulation of various biological processes, such as oxidative stress, DNA damage repair, mitochondrial function, and cellular senescence, which suggests that FOXM1 may play a crucial role in the process of postovulatory aging. Therefore, in this study, we investigated the effects and mechanisms of FOXM1 on oxidative stress, mitochondrial function, DNA damage, and apoptosis during oocyte aging. Our study revealed that aging oocytes exhibited significantly increased ROS levels and significantly decreased GSH, SOD, T-AOC, and CAT levels than did oocytes at the MII stage and that FOXM1 inhibition exacerbated the changes in these levels in aging oocytes. In addition, FOXM1 inhibition increased the levels of DNA damage, apoptosis, and cell senescence in aging oocytes. A p21 inhibitor alleviated the effects of FOXM1 inhibition on oxidative stress, mitochondrial function, and DNA damage and thus alleviated the degree of senescence in aging oocytes. These results indicate that FOXM1 plays a crucial role in porcine oocyte aging. This study contributes to the understanding of the function and mechanism of FOXM1 during porcine oocyte aging and provides a theoretical basis for preventing oocyte aging and optimizing conditions for the in vitro culture of oocytes.

更新日期：2024-08-10

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