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.
Highlights
Cumulus cells, which are layers of specialized granulosa cells encircling oocytes, are thought to be closely related to the growth and meiotic maturation of oocytes, through supplying nutrients or signaling molecules to oocytes via gap junctions [1,2] and via the protection of oocytes from adverse environments or factors [3]
Studies in human and rodent models showed that DSBs increase in oocytes with maternal age, and the corresponding expression of some DSB repair genes decreases in oocytes [23,24]. These findings suggest that an increase in DSBs and a reduced repair capacity in both oocytes and granulosa cells may play a central role in triggering apoptosis and, accelerating ovarian aging [24,25]
Poor oocyte quality is believed to be involved in the impaired developmental potential, the detailed mechanism remains largely unknown
Summary
Cumulus cells, which are layers of specialized granulosa cells encircling oocytes, are thought to be closely related to the growth and meiotic maturation of oocytes, through supplying nutrients or signaling molecules to oocytes via gap junctions [1,2] and via the protection of oocytes from adverse environments or factors [3].
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