Somatic cell-embryo coculture enhances embryo development in vitro by producing embryotrophic factor(s) and/or removing harmful substances from the culture environment. Yet, the underlying molecular mechanisms on how somatic cells remove the toxicants from the culture medium remain largely unknown. By using suppression subtractive hybridization, we identified a number of mouse oviductal genes that were up-regulated when developing preimplantation embryos were present in the oviduct. Epoxide hydrolase 1, microsomal (Ephx1 previously known as mEH) was one of these genes. EPHX1 detoxifies genotoxic compounds and participates in the removal of reactive oxygen species (ROS). The transcript of Ephx1 increases in the oviductal epithelium at the estrus stage and in Day 3 of pregnancy as well as in the uterus of ovariectomized mice injected with estrogen or progesterone. Human oviductal epithelial cells OE-E6/E7 express EPHX1 and improve mouse embryo development in vitro. Addition of an EPHX1 inhibitor, cyclohexene oxide (CHO) or 1,1,1-trichloropropene 2,3-oxide (TCPO), to the culture medium increased intracellular and extracellular ROS levels of OE-E6/E7 cells and suppressed the beneficial effect of the cells on embryo development; CHO and TCPO at these concentrations had no adverse effect on OE-E6/E7 growth and embryo development in vitro. Taken together, EPHX1 in oviductal cells may enhance the development of cocultured embryos by protecting them from oxidative stress. Our result supports the notion that somatic cell coculture may enhance embryo development via removal of deleterious substances in the culture medium.