Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Endocrinology. 2013 Feb;154(2):900-10. doi: 10.1210/en.2012-1967. Epub 2013 Jan 10.
It is well known that withdrawal of progesterone from the maternal circulation is a critical stimulus to parturition in rodents, such as rats and mice. However, mechanisms that determine the timing of progesterone withdrawal are not completely understood. In the present study, we examined whether the vascular endothelial growth factor (VEGF) system in the corpus luteum (CL) contributes to the regulation of circulating progesterone levels and acts as a determinant of the timing of parturition in mice. We found that reduction in the expression levels of VEGF and VEGF receptor-2 in the CL precedes the impairment of luteal circulation and a series of events leading to parturition (i.e., reduction of plasma progesterone, enhancement of myometrium contractility, and onset of parturition). Blocking of VEGF signaling by using the inhibitor of VEGFR tyrosine kinase KRN633 at mid-pregnancy caused a similar sequence of events and induced preterm birth. These results suggest that the VEGF system in the CL plays a critical role in maintaining a high level of circulating progesterone, and determining the timing of parturition in mice.
众所周知，母体循环中孕酮的撤出是啮齿动物（如大鼠和小鼠）分娩的关键刺激因素。然而，决定孕酮撤出时间的机制尚不完全清楚。在本研究中，我们研究了黄体（CL）中的血管内皮生长因子（VEGF）系统是否有助于调节循环孕酮水平，并作为小鼠分娩时间的决定因素。我们发现，CL 中 VEGF 和 VEGF 受体-2 的表达水平降低先于黄体循环受损以及一系列导致分娩的事件（即血浆孕酮减少、子宫肌收缩力增强和分娩开始）。在妊娠中期使用 VEGFR 酪氨酸激酶抑制剂 KRN633 阻断 VEGF 信号会引起类似的事件序列并导致早产。这些结果表明，CL 中的 VEGF 系统在维持高水平循环孕酮和决定小鼠分娩时间方面起着关键作用。
