Exploring potential pathways from oxidative stress to ovarian aging.

Abstract

Aim: In developed nations, women have increasingly deferred childbearing, leading to a rise in demand for infertility treatments and the widespread use of assisted reproductive technologies. However, despite advancements in in vitro fertilization (IVF), live birth rates among women over 40 remain suboptimal. Mitochondrial dysfunction is widely recognized as a key factor in the processes driving the age-related deterioration in both the quantity and quality of oocytes. We aim to summarize current insights into ovarian aging, with a particular focus on pathways that impair mitochondrial function, and explore directions for future research.

Methods: Electronic databases were searched for articles published up to June 30, 2024.

Results: Ongoing ovulation, luteolysis, and menstruation trigger exogenous reactive oxygen species (ROS)-mediated oxidative stress that damages mitochondrial DNA. This, in turn, reduces nuclear gene expression, compromises mitochondrial oxidative phosphorylation, and diminishes adenosine 5' triphosphate production. Persistent endogenous ROS further exacerbate mitochondrial DNA damage and aneuploidy, ultimately causing irreversible chromosomal abnormalities, leading to oocyte aging.

Conclusions: We have delineated the pathway from oxidative stress to ovarian aging. Early detection and management of ovarian aging present challenges and opportunities to enhance IVF treatment strategies.