Abortive expansion of the cumulus and impaired fertility in mice lacking the prostaglandin E receptor subtype EP2 (gene targetingyfertilizationyovulationyprostanoidsygonadotropins)

Female mice lacking the gene encoding the prostaglandin (PG) E2 receptor subtype EP2 (EP2 2y2 ) become pregnant and deliver their pups at term, but with a much reduced litter size. A decrease in ovulation number and a much reduced fertilization rate were observed in EP2 2y2 females without difference of the uterus to support implantation of wild-type embryos. Treatment with gonadotropins induced EP2 mRNA expression in the cumulus cells of ovarian follicles of wild-type mice. The immature cumuli oophori from wild- type mice expanded in vitro in response to both follicle- stimulating hormone and PGE2, but the response to PGE2 was absent in those from EP2 2y2 mice. Cumulus expansion pro- ceeded normally in preovulatory follicles but became abortive in a number of ovulated complexes in EP2 2y2 mice, indicating that EP2 is involved in cumulus expansion in the oviduct in vivo. No difference in the fertilization rate between wild-type and EP2 2y2 mice was found in in vitro studies using cumulus- free oocytes. These results indicate that PGE2 cooperates with gonadotropin to complete cumulus expansion for successful fertilization.