OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Reactive oxygen species in the mammalian pre-implantation embryo

Reactive oxygen species (ROS) occur naturally in pre-implantation embryos as a by-product of ATP generation through oxidative phosphorylation and enzymes such as NADPH oxidase and xanthine oxidase. Biological concentrations of ROS are required for crucial embryonic events such as pronuclear formation, first cleavage and cell proliferation. However, high concentrations of ROS are detrimental to embryo development, resulting in embryo arrest, increased DNA damage and modification of gene expression leading to aberrant fetal growth and health. In vivo embryos are protected against oxidative stress by oxygen scavengers present in follicular and oviductal fluids, while in vitro, embryos rely on their own antioxidant defence mechanisms to protect against oxidative damage, including superoxide dismutase, catalase, glutathione and glutamylcysteine synthestase. Pre-implantation embryonic ROS originate from eggs, sperm and embryos themselves or from the external environment (i.e. in vitro culture system, obesity and ageing). This review examines the biological and pathological roles of ROS in the pre-implantation embryo, maternal and paternal origins of embryonic ROS, and from a clinical perspective, we comment on the growing interest in combating increased oxidative damage in the pre-implantation embryo through the addition of antioxidants.