Reactive Oxygen Species in Embryo Development: Sources, Impacts, and Implications for In Vitro Culture Systems

Reactive oxygen species (ROS) are essential regulators of fertilization and early embryo development in mammals, including humans and various animal models, but they exert detrimental effects when produced in excess. In assisted reproductive technologies (ART), particularly in vitro fertilization (IVF), exposure to non-physiological conditions increases oxidative stress (OS), impairing gamete quality, embryo viability, and clinical outcomes. This review synthesizes experimental and clinical studies describing the endogenous and exogenous sources of ROS relevant to embryo development in IVF. Endogenous ROS arise from intrinsic metabolic pathways such as oxidative phosphorylation, NADPH oxidase, and xanthine oxidase. Exogenous sources include suboptimal laboratory conditions characterized by factors such as high oxygen tension, temperature shifts, pH instability, light exposure, media composition, osmolarity, and cryopreservation procedures. Elevated ROS disrupt oocyte fertilization, embryonic cleavage, compaction, blastocyst formation, and implantation by inducing DNA fragmentation, lipid peroxidation, mitochondrial dysfunction, and apoptosis. In addition, the review highlights how parental health factors establish the initial redox status of gametes, which influences subsequent embryo development in vitro. While antioxidant supplementation and optimized culture conditions can mitigate oxidative injury, the precise optimal redox environment remains a subject of ongoing research. This review emphasizes that future research should focus on defining specific redox thresholds and developing reliable, non-invasive indicators of embryo oxidative status to improve the success rates of ART.