Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, Jilin, P.R. China.
Shenyang Jiuzhou Family Hospital, Shenyang, Liaoning, P.R. China.
PLoS One. 2018 Sep 20;13(9):e0204524. doi: 10.1371/journal.pone.0204524. eCollection 2018.
Women with advanced maternal age exhibit low anti-Müllerian hormone (AMH) levels and an altered follicular environment, which is associated with poor oocyte quality and embryonic developmental potential. However, the underlying mechanism is poorly understood. The present study aimed to assesswhether aging patients exhibit an activated DNA double-strandbreak (DSB) repair pathway in cumulus cells and thus, an association with poor outcomes after in vitro fertilization-embryo transfer (IVF-ET) treatment. Cumulus cells from young (≤29 y) and aging (≥37 y) human female patients were collected after oocyte retrieval. Our results indicated that aging patients showed a higher rate of γ-H2AX-positive cells than in young patients (24.33±4.55 vs.12.40±2.31, P<0.05). We also found that the mRNA expression levels of BRCA1, ATM, MRE11 and RAD51 were significantly elevated in aging cumulus cells. Accordingly, significantly increased protein levels of phospho-H2AX, BRCA1, ATM, MRE11 and RAD51 could be observed in aging cumulus cells. Moreover, aging cumulus cells showed a more frequent occurrence of early apoptosis than young cumulus cells. This study found that increases in DSBs and the activation of the repair pathway are potential indicators that may be used to predictoutcomes after IVF-ET treatment.
高龄产妇表现出低水平的抗苗勒管激素（AMH）和改变的卵泡环境，这与卵子质量差和胚胎发育潜能降低有关。然而，其潜在机制尚不清楚。本研究旨在评估高龄患者的卵丘细胞中是否存在激活的 DNA 双链断裂（DSB）修复途径，以及与体外受精-胚胎移植（IVF-ET）治疗后不良结局的相关性。本研究收集了年轻（≤29 岁）和高龄（≥37 岁）女性患者的卵丘细胞。结果表明，高龄患者的 γ-H2AX 阳性细胞比例高于年轻患者（24.33±4.55 比 12.40±2.31，P<0.05）。我们还发现，高龄卵丘细胞中 BRCA1、ATM、MRE11 和 RAD51 的 mRNA 表达水平显著升高。相应地，高龄卵丘细胞中可观察到磷酸化 H2AX、BRCA1、ATM、MRE11 和 RAD51 的蛋白水平显著升高。此外，高龄卵丘细胞比年轻卵丘细胞更早发生凋亡。本研究发现，DSB 的增加和修复途径的激活可能是预测 IVF-ET 治疗后结局的潜在指标。
