Oxygen, early embryonic metabolism and free radical-mediated embryopathies

Free radicals, once the preserve of chemists, are now recognized as playing a central role in many biological systems. They are formed as an inevitable by-product of aerobic respiration and various cytoplasmic processes at a rate dependent upon the prevailing oxygen tension. At physiological concentrations, oxygen and nitrogen free radical species play key roles in intracellular signalling, regulating many homeostatic mechanisms and mediating stress responses. If concentrations exceed cellular defences, however, then indiscriminate damage may occur to lipids, proteins and DNA. Cell function may be perturbed, and in the most severe cases apoptosis may result. Although there are significant species differences, many aspects of early mammalian development, from fertilization through to differentiation of the principal organ systems, take place in vivo in a low oxygen environment. This may serve to protect the embryo from free radical damage, for exposure of early embryos to ambient oxygen concentrations or the products of maternal metabolic disorders is often associated with reduced viability and an increased rate of congenital malformations. Administration of free radical scavengers, including vitamins C and E, can mitigate many of these effects, indicating the importance of a balanced maternal diet to successful reproduction.