Diversification of cyclooxygenase-2-derived prostaglandins in ovulation and implantation
Diversification of cyclooxygenase-2-derived prostaglandins in ovulation and implantation
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DOI：
10.1095/biolreprod64.5.1557
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发表时间：
2001-05-01
影响因子：
3.6
通讯作者：
Dey, SK
中科院分区：
文献类型：
--
作者：
Matsumoto, H;Ma, WG;Dey, SK
先前在环氧合酶-2（考克斯-2）缺陷小鼠中观察到的排卵和受精缺陷表明，考克斯-2衍生的卵巢前列腺素（PG）参与了这些事件。然而，具体的PG及其作用方式尚不清楚。随后的研究表明，缺乏EP 2（一种PCE 2受体亚型）的小鼠的窝仔数减少，这显然是由于排卵不良，但更明显的是由于受精受损。使用超数排卵方案和体外培养系统，我们在此证明，排卵过程，而不是卵泡生长，卵母细胞成熟，或受精，主要影响成年考克斯-2或EP 2缺陷小鼠。此外，我们的研究结果表明，在体外成熟和受精卵能够随后的植入前发展。然而，成年考克斯-2-或EP 2-缺陷小鼠的排卵严重受损在未成熟（3周龄）的考克斯-2-或EP 2-缺陷小鼠中并未表现出来，这表明成年小鼠的排卵过程更依赖于PG。尽管考克斯-2（-/-）小鼠的着床和蜕膜化过程是有缺陷的，但我们目前的研究结果表明，这些事件在EP 2缺陷小鼠中是正常的，这是通过胚胎移植和实验诱导的蜕膜化来确定的。总的来说，以前和现在的结果表明，考克斯-2衍生的PGE（2）通过激活EP 2对排卵是必需的，而考克斯-2衍生的前列环素通过激活过氧化物酶体增殖物激活受体δ参与着床和蜕膜化。
Previous observations of ovulation and fertilization defects in cyclooxygenase-2 (COX-2)-deficient mice suggested that COX-2-derived ovarian prostaglandins (PGs) participate in these events. However, the specific PG and its mode of action were unknown. Subsequent studies revealed that mice deficient in EP2, a PCE2-receptor subtype, have reduced litter size, apparently resulting from poor ovulation but more dramatically from impaired fertilization. Using a superovulation regimen and in vitro culture system, we demonstrate herein that the ovulatory process, not follicular growth, oocyte maturation, or fertilization, is primarily affected in adult COX-2- or EP2-deficient mice. Furthermore, our results show that in vitro-matured and -fertilized eggs are capable of subsequent preimplantation development. However, severely compromised ovulation in adult COX-2- or EP2-deficient mice is not manifested in immature (3wk-old) COX-2- or EP2-deficient mice, suggesting that the process of ovulation is more dependent on PGs in adult mice. Although the processes of implantation and decidualization are defective in COX-2(-/-) mice, our present results demonstrate that these events are normal in EP2-deficient mice, as determined by embryo transfer and experimentally induced decidualization. Collectively, previous and present results suggest that whereas COX-2-derived PGE(2) is essential for ovulation via activation of EP2, COX-2-derived prostacyclin is involved in implantation and decidualization via activation of peroxisome proliferator-activated receptor delta.