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

Female mice lacking the gene encoding the prostaglandin (PG) E-2 receptor subtype EP2 (EP2-/-) 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-/- 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 wildtype mice expanded in vitro in response to both follicle-stimulating hormone and PGE(2), but the response to PGE(2) was absent in those from EP2-/- mice. Cumulus expansion proceeded normally in preovulatory follicles but became abortive in a number of ovulated complexes in EP2-/- 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-/- mice was found in in vitro studies using cumulusfree oocytes. These results indicate that PGE(2) cooperates with gonadotropin to complete cumulus expansion for successful fertilization.