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

Abstract

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.