I mmature spermatozoa are vulnerable to oxidative stress after their release from the testes, due in part to an innate deficiency in antioxidant enzymes. The male reproductive tract compensates for this deficiency by secreting antioxidant enzymes such as glutathione peroxidase 5 (Gpx5) into the epididymal lumen. In this issue of the JCI, Chabory et al. examined the phenotype of Gpx5^–/– mice and found that while deletion of this gene did not seem to affect fertility per se, it did influence the incidence of miscarriage and embryonic defects in mated wild-type female mice (see the related article beginning on page 2074). Importantly, the appearance of these problems was age dependent and associated with signs of oxidative stress in the spermatozoa. These results demonstrate the key importance of Gpx5 as an extracellular antioxidant designed to protect maturing mammalian spermatozoa from oxidative stress.