Molecular mechanisms for regulation of the corpus luteum function in dairy cows: control of life and death by angiogenesis and angiolysis, and vascular tonus

点击翻译按钮获取中文摘要

This series of study focused on "Luteal Formation" and "Luteal Regression" in the dairy cattle from the window of "angiogenesis and angiolysis" and "vascular tonus", from the views of living animals, luteal tissues, cells, and genes using several experimental models. The major output from this study is as follows;1. Multiple injections of polyclonal antibody against major angiogenic factor VEGF or bFGF directly into the corpus luteum (CL) from immediately after ovulation up to Day 7 inhibited luteal angiogenesis as well as plasma progesterone (P) increase. Both treatments inhibited angiogenesis-and P synthesis-related genes, resulting in the inhibition of CL formation. Furthermore, it was demonstrated that blood supply and angiogenesis relate to "survival and growth" of follicles and CL, while the decrease in blood supply and vessel regression relate to "the death" of these organs.2. We examined in detail the phenomenon discovered by ourselves that "a local boold flow at periphery of mature CL increases prior to the onset of spontaneous luteolysis in the cow". As expected, it became evident that the endothelial cells of large blood vessels surrounding the CL have PGF receptor (FP-R), and NO synthease (NOS) is activated via binding of PGF2a to FP-R, thus endothelial cells release NO molecules locally, inducing vasodilation and the increase in blood flow. These were indicated by several evidence using immunohistochemistry and real-time PCR for relating genes in the CL tissue that obtained at 1 h after PG injection when the CL blood flow increased at maximum. Further evidence was obtaines by the in vivo experiments that direct injections of NO donor into the mid CL induced CL blood flow increase followed by luteolysis and the estrus, and that direct injections of NOS inhibitor blocked CL blood flow increase induced by PG injection and delayed the occurrence of luteolysis.