Abstract
In their midthirties, women experience a decline in fertility, coupled to a pronounced increase in the risk of aneuploidy, miscarriage, and birth defects. Although the aetiology of such pathologies are complex, a causative relationship between the age-related decline in oocyte quality and oxidative stress (OS) is now well established. What remains less certain are the molecular mechanisms governing the increased vulnerability of the aged oocyte to oxidative damage. In this review, we explore the reduced capacity of the ageing oocyte to mitigate macromolecular damage arising from oxidative insults and highlight the dramatic consequences for oocyte quality and female fertility. Indeed, while oocytes are typically endowed with a comprehensive suite of molecular mechanisms to moderate oxidative damage and thus ensure the fidelity of the germline, there is increasing recognition that the efficacy of such protective mechanisms undergoes an age-related decline. For instance, impaired reactive oxygen species metabolism, decreased DNA repair, reduced sensitivity of the spindle assembly checkpoint, and decreased capacity for protein repair and degradation collectively render the aged oocyte acutely vulnerable to OS and limits their capacity to recover from exposure to such insults. We also highlight the inadequacies of our current armoury of assisted reproductive technologies to combat age-related female infertility, emphasising the need for further research into mechanisms underpinning the functional deterioration of the ageing oocyte.
Highlights
The developmental potential of the mammalian oocyte markedly decreases with increasing maternal age, culminating in elevated rates of miscarriage, birth defects, and reduced fertility [1,2,3,4]
Traditional paradigms hold that the primary mechanism behind the age-related decline in oocyte quality is the accumulation of spontaneous damage to the mitochondria arising from reactive oxygen species (ROS) produced by the mitochondria themselves during daily biological metabolism [36]
Given the electron leakage associated with mitochondrial damage, it could be assumed that the oxidative burden is reduced upon germinal vesicle transfer (GVT) of aged oocytes into young ooplasts and leads us to once again highlight the contribution of oxidative stress (OS) to the age-related deterioration of the oocyte
Summary
The developmental potential of the mammalian oocyte markedly decreases with increasing maternal age, culminating in elevated rates of miscarriage, birth defects, and reduced fertility [1,2,3,4]. This loss of fecundity becomes evident when a woman reaches her midthirties. The need to elucidate the mechanisms by which advanced maternal age negatively affects oocyte quality has become pressing owing to the recent trend for women in developed countries to delay child bearing several years beyond that of their peak reproductive capacity. We discuss the current means by which OS can be prevented or delayed in older mothers
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