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

Abortive expansion of the cumulus and impaired fertility in mice lacking the prostaglandin E receptor subtype EP2
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DOI:
10.1073/pnas.96.18.10501
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发表时间:
1999-08-31
影响因子:
11.1
通讯作者:
Ichikawa, A
Ichikawa, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hizaki, H;Segi, E;Ichikawa, A

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缺乏编码前列腺素 (PG) E-2 受体亚型 EP2 (EP2-/-) 基因的雌性小鼠会怀孕并足月产下幼崽,但产仔数大大减少。在没有子宫差异以支持野生型胚胎植入的EP2-/-雌性中观察到排卵次数减少和受精率大大降低。促性腺激素治疗诱导野生型小鼠卵泡卵丘细胞中 EP2 mRNA 的表达。野生型小鼠的未成熟卵丘在体外对卵泡刺激素和 PGE(2) 均有反应,但在 EP2-/- 小鼠中不存在对 PGE(2) 的反应。卵丘扩张在排卵前卵泡中正常进行,但在 EP2-/- 小鼠的许多排卵复合体中变得失败,表明 EP2 参与体内输卵管的卵丘扩张。在使用无卵丘卵母细胞的体外研究中,未发现野生型小鼠和 EP2-/- 小鼠之间的受精率存在差异。这些结果表明PGE(2)与促性腺激素配合完成卵丘扩张以成功受精。
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.