Female infertility is a growing concern in developed countries as delayed childbearing and ovarian dysfunction become more common. Ovarian decline is characterized by follicular depletion, granulosa cell dysfunction, aneuploidy, spindle assembly defects, mitochondrial damage, DNA damage, telomere shortening, stromal remodeling, and cellular senescence. Current approaches (hormonal therapy, assisted reproductive technologies, platelet-rich plasma, stem cells, extracellular vesicles, and mitochondrial-targeted treatments) offer partial benefit but do not directly correct the molecular drivers of ovarian dysfunction. Gene therapy via viral vectors offers a more direct strategy. Adeno-associated virus serotype 9 (AAV9) is attractive for its broad tropism, long-term transgene expression, favorable safety profile, and evidence of ovarian somatic cell transduction, particularly in granulosa and interstitial cells. It remains experimental, however, and requires rigorous evaluation of biodistribution, immune response, off-target effects, germline safety, embryo development, offspring health, and tumorigenic risk. This review summarizes the mechanisms of ovarian dysfunction, current therapeutic limitations, AAV9’s advantages, delivery routes, candidate genes, and translational safety concerns.

Maternal aging is associated with increased oxidative stress and decreased mitochondrial function, which deteriorate oocyte quality. Ginsenoside Re (GRe), an antioxidant derived from Panax ginseng, has been reported to alleviate cellular damage and extend healthy lifespan. In this study, we investigated the protective effects of GRe on in vitro-matured bovine oocytes and elucidated the underlying mechanisms. Oocyte aging-like oxidative stress conditions were induced by adding 20 mg/mL D-galactose (D-gal) to the in vitro maturation (IVM) medium; GRe treatment involved supplementing the medium with various GRe concentrations (25, 50, and 100 μg/mL). GRe treatment significantly improved maturation, with 50 μg/mL GRe showing the most pronounced effect. This recovery was accompanied by reduced accumulation of reactive oxygen species and improved mitochondrial capacity and biogenesis, mediated by SIRT1/Nrf2 signaling. Consequently, GRe improved embryonic developmental ability. These findings suggest that GRe may improve oocyte quality in the context of aging and associated oxidative stress.