Hizaki H, Segi E, Sugimoto Y, Hirose M, Saji T, Ushikubi F, Matsuoka T, Noda Y, Tanaka T, Yoshida N, Narumiya S, Ichikawa A
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10501-6. doi: 10.1073/pnas.96.18.10501.
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.
缺乏编码前列腺素（PG）E2受体亚型EP2（EP2-/-）基因的雌性小鼠能够正常怀孕并足月产仔，但产仔数明显减少。在EP2-/-雌性小鼠中观察到排卵数量减少和受精率大幅降低，而其子宫支持野生型胚胎着床的能力并无差异。用促性腺激素处理可诱导野生型小鼠卵巢卵泡卵丘细胞中EP2 mRNA表达。野生型小鼠的未成熟卵丘卵母细胞复合体在体外对促卵泡激素和PGE2均有反应而发生扩展，但EP2-/-小鼠的未成熟卵丘卵母细胞复合体对PGE2无反应。卵丘扩展在排卵前卵泡中正常进行，但在EP2-/-小鼠的一些排卵复合体中失败，这表明EP2参与体内输卵管中的卵丘扩展。在使用无卵丘卵母细胞的体外研究中，未发现野生型和EP2-/-小鼠之间受精率有差异。这些结果表明，PGE2与促性腺激素协同作用以完成卵丘扩展从而实现成功受精。
