University of Coimbra, Institute for Interdisciplinary Research, PhD Programme in Experimental Biology and Biomedicine (PDBEB), 3030-789 Coimbra, Portugal.
University of Coimbra, CNC-UC-Centre for Neuroscience and Cell Biology, 3004-504 Coimbra, Portugal.
Biomolecules. 2024 Feb 26;14(3):281. doi: 10.3390/biom14030281.
Age-related changes in the mitochondrial status of human cumulus cells (hCCs) impact oocyte quality; however, the relationship between hCC mitochondrial (dys)function and reproductive aging remains poorly understood. This study aimed to establish the interplay between hCC mitochondrial dysfunction and women's reproductive potential. In this investigation, 266 women were enrolled and categorized into two groups based on their age: a young group (<35 years old) and an advanced maternal age (AMA) group (≥35 years old). Comprehensive analysis of reproductive outcomes was conducted in our population. Various mitochondrial-related parameters were analyzed across distinct subsets. Specifically, mitochondrial membrane potential (∆Ψm) and mitochondrial mass were examined in 53 samples, mtDNA content in 25 samples, protein levels in 23 samples, bioenergetic profiles using an XF24 Extracellular Flux Analyzer in 6 samples, and levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in 39 and 43 samples, respectively. In our study, the reproductive potential of AMA women sharply decreased, as expected. Additionally, an impairment in the mitochondrial function of hCCs in older women was observed; however, no differences were found in terms of mitochondrial content. Regarding oxidative phosphorylation, metabolic profiling of hCCs from AMA women indicated a decrease in respiratory capacity, which was correlated with an age-dependent decrease in the ATP synthase (ATP5A1) protein level. However, intracellular ROS and ATP levels did not differ between groups. In conclusion, our study indicates that age-related dysfunction in hCCs is associated with impaired mitochondrial function, and, although further studies are required, ATP synthase could be relevant in this impairment.
随着人卵丘细胞（hCC）中线粒体状态的衰老变化，会影响卵母细胞的质量；然而，hCC 线粒体（功能）障碍与生殖衰老之间的关系仍知之甚少。本研究旨在建立 hCC 线粒体功能障碍与女性生殖潜能之间的相互关系。在这项研究中，我们招募了 266 名女性，并根据年龄将其分为两组：年轻组（<35 岁）和高龄产妇组（≥35 岁）。我们对人群的生殖结局进行了综合分析。对不同亚组进行了各种线粒体相关参数的分析。具体来说，我们检测了 53 个样本中的线粒体膜电位（∆Ψm）和线粒体质量、25 个样本中的 mtDNA 含量、23 个样本中的蛋白质水平、6 个样本中的 XF24 细胞外通量分析仪中的生物能谱以及 39 个样本中的活性氧（ROS）和 43 个样本中的三磷酸腺苷（ATP）水平。在我们的研究中，高龄产妇女性的生殖潜能如预期般明显下降。此外，我们观察到年长女性 hCC 中线粒体功能受损，但线粒体含量没有差异。关于氧化磷酸化，高龄产妇 hCC 的代谢特征表明呼吸能力下降，这与 ATP 合酶（ATP5A1）蛋白水平随年龄的下降有关。然而，两组之间的细胞内 ROS 和 ATP 水平没有差异。总之，我们的研究表明，hCC 与年龄相关的功能障碍与线粒体功能障碍有关，尽管还需要进一步的研究，但 ATP 合酶可能与此类损伤有关。
