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

H Hizaki, E Segi, Y Sugimoto… - Proceedings of the …, 1999 - National Acad Sciences
H Hizaki, E Segi, Y Sugimoto, M Hirose, T Saji, F Ushikubi, T Matsuoka, Y Noda, T Tanaka…
Proceedings of the National Academy of Sciences, 1999National Acad Sciences
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 …
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.
National Acad Sciences