Oxidative Stress and Mitochondrial Dysfunction in Reproductive Aging: From Oocyte Quality to Fertility Decline

Reproductive aging is one of the most time-sensitive biological processes in mammals. Female fertility begins to decline sharply from the mid-thirties, driven by a progressive deterioration in oocyte quality that precedes and predicts the broader collapse of reproductive capacity. At the cellular level, this decline is now understood through the converging lenses of oxidative stress and mitochondrial dysfunction - two fundamental hallmarks of aging that bear with particular force on the female reproductive system.Oocytes are among the longest-lived cells in the human body, remaining in a state of arrested meiosis for decades before ovulation. This extraordinary lifespan renders them uniquely vulnerable to the cumulative effects of reactive oxygen species (ROS) accumulation, mitochondrial DNA damage, and impaired energy metabolism. As women age, declining antioxidant defenses and reduced mitochondrial biogenesis compromise oocyte competence, contributing to chromosomal instability, poor fertilization rates, and elevated rates of embryo aneuploidy. Beyond the oocyte itself, mitochondrial dysfunction reshapes the broader reproductive microenvironment - including granulosa cells, cumulus cells, and follicular fluid - generating a redox-imbalanced niche that further impairs folliculogenesis and accelerates ovarian reserve depletion.Systemic metabolic shifts add another layer of complexity. Altered NAD+ metabolism, dysregulated mitophagy, impaired mTOR signaling, and changes in lipid and glucose homeostasis are increasingly recognized as key contributors to age-related fertility decline, linking reproductive aging to the wider field of metabolic geroscience.This Research Topic invites original research articles, reviews, and perspectives that explore the molecular and cellular mechanisms at the intersection of oxidative stress, mitochondrial biology, and reproductive aging. Topics of interest include, but are not limited to:- Redox regulation of oocyte maturation and follicle development- Mitochondrial dynamics, biogenesis, and quality control in reproductive cells- Metabolic reprogramming and energy homeostasis during ovarian aging- Antioxidant and mitochondria-targeted interventions to support fertility- Biomarkers of oxidative damage and mitochondrial health in reproductive aging- Translational strategies to extend reproductive longevity- Contributions exploring related aspects of reproductive aging not listed above are equally welcome, provided they align with the overarching focus of the collection.By bridging reproductive biology, redox biochemistry, and geroscience, this collection aims to deepen our mechanistic understanding of fertility decline and catalyze the development of evidence-based interventions to preserve reproductive health across the lifespan. Topic editors: Kadiliya Jueraitetibaike, Rujun Ma, Jie Dong Source: https://www.frontiersin.org/research-topics/82432/oxidative-stress-and-mitochondrial-dysfunction-in-reproductive-aging-from-oocyte-quality-to-fertility-decline