Embryonic genome activation (EGA) is a critical step during embryonic development. Several transcription factors have been identified that play major roles in initiating EGA; however, this gradual and complex mechanism still needs to be explored. In this study, we investigated the role of nuclear transcription factor Y subunit A (NFYA) in bovine EGA and bovine embryonic development and its relationship with the platelet-derived growth factor receptor-β (PDGFRβ) by using a potent selective activator (PDGF-BB) and inhibitor (CP-673451) of PDGF receptors. Activation and inhibition of PDGFRβ using PDGF-BB and CP-673451 revealed that NFYA expression is significantly (p < 0.05) affected by the PDGFRβ. In addition, PDGFRβ mRNA expression was significantly increased (p < 0.05) in the activator group and significantly decreased (p < 0.05) in the inhibitor group when compared with PDGFRα. Downregulation of NFYA following PDGFRβ inhibition was associated with the expression of critical EGA-related genes, bovine embryo development rate, and implantation potential. Moreover, ROS and mitochondrial apoptosis levels and expression of pluripotency-related markers necessary for inner cell mass development were also significantly (p < 0.05) affected by the downregulation of NFYA while interrupting trophoblast cell (CDX2) differentiation. In conclusion, the PDGFRβ-NFYA axis is critical for bovine embryonic genome activation and embryonic development.

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.