Progesterone, but not estrogen, stimulates vessel maturation in the mouse endometrium
Progesterone, but not estrogen, stimulates vessel maturation in the mouse endometrium
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DOI：
10.1210/en.2007-0856
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发表时间：
2007-11-01
期刊：
影响因子：
4.8
通讯作者：
Rogers, Peter A. W.
中科院分区：
文献类型：
--
作者：
Girling, Jane E.;Lederman, Fiona L.;Rogers, Peter A. W.
人子宫内膜经历规律的生长和退化期，包括脉管系统的伴随变化，并且是在常规生理基础上发生显著血管生成和血管成熟的少数成人组织之一。本研究旨在探讨雌、孕激素对小鼠子宫内膜血管成熟的影响。从早期妊娠小鼠（d 1-4）和卵巢切除小鼠收集子宫内膜组织，所述小鼠在解剖前24小时给予单次17 β-雌二醇（100 ng）注射（短期雌激素方案）或连续三次每天注射孕酮（1 mg），有/没有雌激素引发（孕酮方案）。然后重复实验，包括同时用孕酮和RU 486或血管内皮生长因子-A抗血清治疗的小鼠。在妊娠第3-4天，可观察到血管壁细胞（PVMC）的增加，这与循环孕酮的增加相对应。与对照组相比，在用孕酮处理的小鼠中观察到血管轮廓的PVMC和α-平滑肌肌动蛋白（标签壁细胞）覆盖的显著增加;在用雌激素或血管内皮生长因子抗血清处理的小鼠中没有观察到显著变化。RU 486治疗没有抑制炔雌醇诱导的PVMC和壁细胞覆盖的增加，虽然炔雌醇诱导的内皮细胞和上皮细胞增殖的变化受到抑制。这些结果表明，孕激素，而不是雌激素，刺激血管成熟的小鼠子宫内膜。这项工作说明了小鼠模型的相关性，了解子宫内膜血管重塑在月经周期和临床上重要的孕激素受体拮抗剂RU 486。
The human endometrium undergoes regular periods of growth and regression, including concomitant changes in the vasculature, and is one of the few adult tissues where significant angiogenesis and vascular maturation occurs on a routine, physiological basis. The aim of this study was to investigate the effects of estrogen and progesterone on endometrial vascular maturation in mice. Endometrial tissues were collected from early pregnant mice (d 1-4) and ovariectomized mice given a single 17 beta-estradiol (100 ng) injection 24 h before dissection (short-term estrogen regime) or three consecutive daily injections of progesterone (1 mg) with/without estrogen priming (progesterone regime). Experiments were then repeated with the inclusion of mice treated concurrently with progesterone and either RU486 or a vascular endothelial growth factor-A antiserum. Proliferating vascular mural cells (PVMC) were observed on d 3-4 of pregnancy, corresponding with an increase in circulating progesterone. A significant increase in PVMC and alpha-smooth muscle actin (labels mural cells) coverage of vessel profiles were observed in mice treated with progesterone in comparison to controls; no significant change was noted in mice treated with estrogen or with vascular endothelial growth factor antiserum. RU486 treatment did not inhibit the progesterone-induced increases in PVMC and mural cell coverage, although progesterone-induced changes in endothelial and epithelial cell proliferation were inhibited. These results show that progesterone, but not estrogen, stimulates vessel maturation in the mouse endometrium. The work illustrates the relevancy of the mouse model for understanding endometrial vascular remodeling during the menstrual cycle and in response to the clinically important progesterone receptor antagonist RU486.