Girling Jane E, Rogers Peter A W
Centre for Women's Health Research, Monash University Department of Obstetrics and Gynaecology, Monash Medical Centre, Clayton, Victoria, Australia.
Angiogenesis. 2005;8(2):89-99. doi: 10.1007/s10456-005-9006-9. Epub 2005 Oct 7.
This review summarises recent research into the mechanisms and regulation of endometrial angiogenesis. Understanding of when and by what mechanisms angiogenesis occurs during the menstrual cycle is limited, as is knowledge of how it is regulated. Significant endometrial endothelial cell proliferation occurs at all stages of the menstrual cycle in humans, unlike most animal models where a more precise spatial relationship exists between endothelial cell proliferation and circulating levels of oestrogen and progesterone. Recent stereological data has identified vessel elongation as a major endometrial angiogenic mechanism in the mid-late proliferative phase of the cycle. In contrast, the mechanisms that contribute to post-menstrual repair and secretory phase remodelling have not yet been determined. Both oestrogen and progesterone/progestins appear to have paradoxical actions, with recent studies showing that under different circumstances both can promote as well as inhibit endometrial angiogenesis. The relative contribution of direct versus indirect effects of these hormones on the vasculature may help to explain their pro- or anti-angiogenic activities. Recent work has also identified the hormone relaxin as a player in the regulation of endometrial angiogenesis. While vascular endothelial growth factor (VEGF) is fundamental to endometrial angiogenesis, details of how and when different endometrial cell types produce VEGF, and how production and activity is controlled by oestrogen and progesterone, remains to be elucidated. Evidence is emerging that the different splice variants of VEGF play a major role in regulating endometrial angiogenesis at a local level. Intravascular neutrophils containing VEGF have been identified as having a role in stimulating endometrial angiogenesis, although other currently unidentified mechanisms must also exist. Future studies to clarify how endometrial angiogenesis is regulated in the human, as well as in relevant animal models, will be important for a better understanding of diseases such as breakthrough bleeding, menorrhagia, endometriosis and endometrial cancer.
本综述总结了近期关于子宫内膜血管生成机制及调控的研究。对于血管生成在月经周期中何时以及通过何种机制发生的理解有限，对其调控方式的了解也同样如此。与大多数动物模型不同，在人类月经周期的所有阶段都会发生显著的子宫内膜内皮细胞增殖，在这些动物模型中，内皮细胞增殖与雌激素和孕激素的循环水平之间存在更精确的空间关系。最近的体视学数据已确定血管伸长是月经周期中晚期增殖期的主要子宫内膜血管生成机制。相比之下，对月经后修复和分泌期重塑的机制尚未确定。雌激素和孕激素/孕激素似乎具有矛盾的作用，最近的研究表明，在不同情况下，它们既可以促进也可以抑制子宫内膜血管生成。这些激素对脉管系统的直接和间接作用的相对贡献可能有助于解释它们的促血管生成或抗血管生成活性。最近的研究还确定激素松弛素是子宫内膜血管生成调控中的一个参与者。虽然血管内皮生长因子（VEGF）对子宫内膜血管生成至关重要，但不同子宫内膜细胞类型如何以及何时产生VEGF，以及其产生和活性如何受雌激素和孕激素控制的细节仍有待阐明。越来越多的证据表明，VEGF的不同剪接变体在局部调节子宫内膜血管生成中起主要作用。已确定含有VEGF的血管内中性粒细胞在刺激子宫内膜血管生成中起作用，尽管肯定还存在其他目前尚未明确的机制。未来的研究旨在阐明人类以及相关动物模型中子宫内膜血管生成是如何调控的，这对于更好地理解诸如突破性出血、月经过多、子宫内膜异位症和子宫内膜癌等疾病至关重要。
