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

Abstract

Female mice lacking the gene encoding the prostaglandin (PG) E₂ 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 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 ^−/− 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 cumulus-free oocytes. These results indicate that PGE₂ cooperates with gonadotropin to complete cumulus expansion for successful fertilization.

• gene targeting
• fertilization
• ovulation
• prostanoids
• gonadotropins