Daugelaite Klaudija, Lacour Perrine, Winkler Ivana, Koch Marie-Luise, Schneider Anja, Schneider Nina, Coraggio Francesca, Tolkachov Alexander, Nguyen Xuan Phuoc, Vilkaite Adriana, Rehnitz Julia, Odom Duncan T, Goncalves Angela
Division of Regulatory Genomics and Cancer Evolution, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Faculty of Biosciences, Ruprecht-Karl-University Heidelberg, Heidelberg, Germany.
Nat Commun. 2025 Apr 17;16(1):3658. doi: 10.1038/s41467-025-58451-9.
In vitro fertilization efficiency is limited in part because a fraction of retrieved oocytes fails to fertilize. Accurately evaluating their quality could significantly improve in vitro fertilization efficiency, which would require better understanding how their maturation may be disrupted. Here, we quantitatively investigate the interplay between superovulation and aging in mouse oocytes and their paired granulosa cells using a newly adapted experimental methodology. We test the hypothesis that superovulation disrupts oocyte maturation, revealing the key intercellular communication pathways dysregulated at the transcriptional level by forced hormonal stimulation. We further demonstrate that granulosa cell transcriptional markers can prospectively predict an associated oocyte's early developmental potential. By using naturally ovulated old mice as a non-stimulated reference, we show that aging and superovulation dysregulate similar genes and interact with each other. By comparing mice and human transcriptional responses of granulosa cells, we find that age-related dysregulation of hormonal responses and cell cycle pathways are shared, though substantial divergence exists in other pathways.
体外受精效率受到限制，部分原因是回收的卵母细胞中有一部分未能受精。准确评估它们的质量可以显著提高体外受精效率，而这需要更好地了解它们的成熟过程是如何被破坏的。在这里，我们使用一种新改进的实验方法，定量研究小鼠卵母细胞及其配对的颗粒细胞中超排卵与衰老之间的相互作用。我们检验了超排卵会破坏卵母细胞成熟的假设，揭示了在强制激素刺激下转录水平失调的关键细胞间通讯途径。我们进一步证明，颗粒细胞转录标志物可以前瞻性地预测相关卵母细胞的早期发育潜力。通过使用自然排卵的老龄小鼠作为非刺激对照，我们表明衰老和超排卵会使相似的基因失调并相互作用。通过比较小鼠和人类颗粒细胞的转录反应，我们发现激素反应和细胞周期途径中与年龄相关的失调是共有的，尽管在其他途径中存在很大差异。
