Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan.
Reproduction. 2012 Apr;143(4):491-500. doi: 10.1530/REP-11-0465. Epub 2012 Feb 24.
The development of the corpus luteum (CL), which secretes large amounts of progesterone to establish pregnancy, is accompanied by active angiogenesis, vascularization, and lymphangiogenesis. Negative feedback regulation is a critical physiological mechanism. Vasohibin-1 (VASH1) was recently discovered as a novel endothelium-derived negative feedback regulator of vascularization. We therefore investigated the expression of VASH1 in the bovine CL. Expression of VASH1 mRNA and protein was predominantly localized to luteal endothelial cells (LECs). VASH1 expression in the CL was constant through the early to late luteal phases and decreased during CL regression relating with the action of luteolytic prostaglandin F(2)(α) in vivo. To investigate the role of VASH1, we determined whether VASH1 treatment affects angiogenesis and/or lymphangiogenesis using LECs and lymphatic endothelial cells (LyECs) in vitro. Vascular endothelial growth factor A (VEGFA) stimulated the expression of VASH1 in LECs but not in LyECs, and VASH1 completely blocked VEGFA-induced formation of capillary-like tube structures of LECs and LyECs in vitro. In summary, VASH1 is predominantly located on LECs in the bovine CL and inhibits the angiogenic and lymphangiogenic actions of VEGFA. Bovine CL therefore has a VEGFA-VASH1 system that may be involved in regulation of luteal function, especially in the development of the CL. The results indicate that VASH1 has the potential to act as a negative feedback regulator of angiogenesis and lymphangiogenesis in the CL in cows.
黄体（CL）的发育伴随着大量孕激素的分泌以维持妊娠，同时伴随着活跃的血管生成、血管化和淋巴管生成。负反馈调节是一种关键的生理机制。血管抑肽-1（VASH1）最近被发现是一种新的内皮衍生的血管生成负反馈调节剂。因此，我们研究了 VASH1 在牛黄体中的表达。VASH1mRNA 和蛋白的表达主要定位于黄体内皮细胞（LEC）。VASH1 在黄体中的表达在黄体早期到晚期保持不变，在黄体退化期间下降，这与体内黄体溶解前列腺素 F（2）（α）的作用有关。为了研究 VASH1 的作用，我们通过体外培养黄体内皮细胞（LEC）和淋巴管内皮细胞（LyEC）来确定 VASH1 处理是否影响血管生成和/或淋巴管生成。血管内皮生长因子 A（VEGFA）刺激 LEC 中 VASH1 的表达，但不刺激 LyEC 中 VASH1 的表达，VASH1 完全阻断 VEGFA 诱导的 LEC 和 LyEC 体外形成毛细血管样管状结构。总之，VASH1 主要位于牛黄体的 LEC 上，并抑制 VEGFA 的血管生成和淋巴管生成作用。因此，牛黄体具有 VEGFA-VASH1 系统，可能参与黄体功能的调节，特别是黄体的发育。结果表明，VASH1 有可能作为牛黄体中血管生成和淋巴管生成的负反馈调节剂。
