Research and Development, EUGIN Group, Barcelona, Spain.
School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
Mol Hum Reprod. 2024 Jun 26;30(7). doi: 10.1093/molehr/gaae023.
Advanced maternal age is associated with a decline in oocyte quality, which often leads to reproductive failure in humans. However, the mechanisms behind this age-related decline remain unclear. To gain insights into this phenomenon, we applied plexDIA, a multiplexed data-independent acquisition, single-cell mass spectrometry method, to analyze the proteome of oocytes from both young women and women of advanced maternal age. Our findings primarily revealed distinct proteomic profiles between immature fully grown germinal vesicle and mature metaphase II oocytes. Importantly, we further show that a woman's age is associated with changes in her oocyte proteome. Specifically, when compared to oocytes obtained from young women, advanced maternal age oocytes exhibited lower levels of the proteasome and TRiC complex, as well as other key regulators of proteostasis and meiosis. This suggests that aging adversely affects the proteostasis and meiosis networks in human oocytes. The proteins identified in this study hold potential as targets for improving oocyte quality and may guide future studies into the molecular processes underlying oocyte aging.
高龄与卵母细胞质量下降有关，这往往导致人类生殖失败。然而，这种与年龄相关的下降的机制仍不清楚。为了深入了解这一现象，我们应用 plexDIA（一种多重数据非依赖采集、单细胞质谱方法）分析了年轻女性和高龄女性卵母细胞的蛋白质组。我们的研究结果主要揭示了未成熟完全生长的生发泡和成熟的中期 II 卵母细胞之间明显不同的蛋白质组特征。重要的是，我们进一步表明女性的年龄与卵母细胞蛋白质组的变化有关。具体来说，与从年轻女性获得的卵母细胞相比，高龄产妇的卵母细胞中蛋白酶体和 TRiC 复合物的水平较低，以及其他参与蛋白质稳态和减数分裂的关键调节剂的水平也较低。这表明衰老对人类卵母细胞的蛋白质稳态和减数分裂网络有不利影响。本研究中鉴定的蛋白质可能作为改善卵母细胞质量的靶点，并可能指导未来对卵母细胞衰老相关分子过程的研究。
