Abortive expansion of the cumulus and impaired fertility in mice lacking the prostaglandin E receptor subtype EP(2).
Female mice lacking the gene encoding the prostaglandin (PG) E(2) receptor subtype EP(2) (EP(2)(-/-)) 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 EP(2)(-/-) females without difference of the uterus to support implantation of wild-type embryos. Treatment with gonadotropins induced EP(2) 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 PGE(2), but the response to PGE(2) was absent in those from EP(2)(-/-) mice. Cumulus expansion proceeded normally in preovulatory follicles but became abortive in a number of ovulated complexes in EP(2)(-/-) mice, indicating that EP(2) is involved in cumulus expansion in the oviduct in vivo. No difference in the fertilization rate between wild-type and EP(2)(-/-) mice was found in in vitro studies using cumulus-free oocytes. These results indicate that PGE(2) cooperates with gonadotropin to complete cumulus expansion for successful fertilization.
Hizaki
H
H
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Segi
E
E
Sugimoto
Y
Y
Hirose
M
M
Saji
T
T
Ushikubi
F
F
Matsuoka
T
T
Noda
Y
Y
Tanaka
T
T
Yoshida
N
N
Narumiya
S
S
Ichikawa
A
A
D000022:Abortion, Spontaneous / Q000235:genetics*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000494:pharmacology; D004624:Embryo Transfer; D005260:Female; D005306:Fertilization; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007247:Infertility, Female / Q000235:genetics* / Q000503:physiopathology; D007527:Isoenzymes / Q000235:genetics; D008098:Litter Size; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism*; D010060:Ovulation; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D018078:Receptors, Prostaglandin E / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D014158:Transcription, Genetic / Q000187:drug effects
D006063:Chorionic Gonadotropin; D007527:Isoenzymes; C545645:Ptger2 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D005640:Follicle Stimulating Hormone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone