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The activated DNA double-strand break repair pathway in cumulus cells from aging patients may be used as a convincing predictor of poor outcomes after in vitro fertilization-embryo transfer treatment
PLOS ONE ( IF 3.7 ) Pub Date : 2018-09-20 , DOI: 10.1371/journal.pone.0204524
Xu-lei Sun , Hao Jiang , Dong-xu Han , Yao Fu , Jian-bo Liu , Yan Gao , Shu-min Hu , Bao Yuan , Jia-bao Zhang

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.



中文翻译:

衰老患者卵丘细胞中活化的DNA双链断裂修复途径可作为体外受精-胚胎移植治疗后不良结局的有力预测指标

产妇高龄的妇女表现出较低的抗苗勒氏激素(AMH)水平和改变的卵泡环境,这与不良的卵母细胞质量和胚胎发育潜能有关。但是,人们对这种潜在的机制知之甚少。本研究旨在评估衰老患者是否在卵丘细胞中显示出活化的DNA双链断裂(DSB)修复途径,从而与体外受精-胚胎移植(IVF-ET)治疗后的不良预后相关。取卵后,收集年轻(≤29岁)和老年(≥37岁)女性患者的积聚细胞。我们的结果表明,衰老患者的γ-H2AX阳性细胞比率高于年轻患者(24.33±4.55 vs.12.40±2.31,P <0.05)。我们还发现BRCA1,ATM,MRE11和RAD51在衰老的卵丘细胞中显着升高。因此,在衰老的卵丘细胞中可以观察到磷酸化H2AX,BRCA1,ATM,MRE11和RAD51的蛋白质水平显着增加。此外,衰老的卵丘细胞比年轻的卵丘细胞显示出更频繁的早期凋亡发生。这项研究发现,DSB的增加和修复途径的激活是可能的指标,可用于预测IVF-ET治疗后的结果。

更新日期:2018-09-21
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