Lebovic D I, Shifren J L, Ryan I P, Mueller M D, Korn A P, Darney P D, Taylor R N
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143-0556, USA.
Hum Reprod. 2000 Aug;15 Suppl 3:67-77. doi: 10.1093/humrep/15.suppl_3.67.
A key mechanism underlying the cyclical growth of the endometrium is its ability to regenerate a vascular capillary network. In normal cycling human endometrium, angiogenesis is influenced by both endocrine and paracrine factors. Hormonal manipulation of the endometrium, such as that occurring during the use of steroidal contraception, appears to result in capillary proliferation and fragility. As a consequence of these vascular changes, contraceptive users may be predisposed to unpredictable uterine bleeding, which is responsible for the high frequency of contraceptive discontinuation. In this paper we address mechanisms responsible for vascular endothelial cell proliferation in normal and contraceptive steroid-exposed endometria. We propose that regulation of endometrial angiogenesis is mediated indirectly, via steroid and cytokine actions on vascular endothelial growth factor (VEGF), and we present data indicating that VEGF expression in normal endometrial stromal cells is increased by oestrogens and progestins. Three proinflammatory cytokines with angiogenic effects in other systems (i.e. interleukin-1beta, tumour necrosis factor-alpha and interferon-gamma) do not appear to up-regulate VEGF expression in normal endometrial stromal cells. Well-characterized in-vitro models in conjunction with immunohistochemistry provide useful experimental systems to study endometrial neovascularization under physiological conditions and in those potentially perturbed via the use of contraceptive steroids.
子宫内膜周期性生长的一个关键机制是其再生血管毛细血管网络的能力。在正常月经周期的人类子宫内膜中，血管生成受内分泌和旁分泌因子的影响。对子宫内膜的激素调控，如在使用甾体避孕药期间发生的情况，似乎会导致毛细血管增殖和脆弱性增加。这些血管变化的结果是，避孕药使用者可能易发生不可预测的子宫出血，这也是避孕药停用率高的原因。在本文中，我们探讨了正常子宫内膜和暴露于避孕甾体激素的子宫内膜中血管内皮细胞增殖的机制。我们提出，子宫内膜血管生成的调节是通过甾体激素和细胞因子对血管内皮生长因子（VEGF）的作用间接介导的，并且我们提供的数据表明，雌激素和孕激素可增加正常子宫内膜基质细胞中VEGF的表达。在其他系统中具有血管生成作用的三种促炎细胞因子（即白细胞介素-1β、肿瘤坏死因子-α和干扰素-γ）似乎不会上调正常子宫内膜基质细胞中VEGF的表达。结合免疫组织化学的特征明确的体外模型为研究生理条件下以及因使用避孕甾体激素而可能受到干扰的情况下的子宫内膜新生血管形成提供了有用的实验系统。
