Furuya Mitsuko, Ishida Junji, Aoki Ichiro, Fukamizu Akiyoshi
Department of Pathology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa, Yokohama, Japan.
Vasc Health Risk Manag. 2008;4(6):1301-13. doi: 10.2147/vhrm.s4009.
During embryogenesis and development, the fetus obtains oxygen and nutrients from the mother through placental microcirculation. The placenta is a distinctive organ that develops and differentiates per se, and that organizes fetal growth and maternal condition in the entire course of gestation. Several life-threatening diseases during pregnancy, such as pregnancy-induced hypertension (PIH) and eclampsia, are closely associated with placental dysfunction. Genetic susceptibilities and poor placentation have been investigated intensively to understand the pathophysiology of PIH. It is currently thought that "poor placentation hypothesis", in which extravillous trophoblasts fail to invade sufficiently the placental bed, explains in part maternal predisposition to this disease. Cumulative studies have suggested that hypoxic micromilieu of fetoplacental site, shear stress of uteroplacental blood flow, and aberrantly secreted proinflammatory substances into maternal circulation synergistically contribute to the progression of PIH. For example, soluble form of vascular endothelial growth factor receptor-1 (sVEGFR-1) and soluble form of CD105 are elevated in circulation of PIH mothers. However, it remains to be poorly understood the pathological events in the placenta during the last half of gestation as maternal systemic disorders get worse. For better understanding and effective therapeutic approaches to PIH, it is important to clarify pathological course of PIH-associated changes in the placenta. In this review, current understanding of placental development and the pathophysiology of PIH placenta are summarized. In addition, recent findings of vasoactive signalings in PIH and rodent PIH models are discussed.
在胚胎发生和发育过程中，胎儿通过胎盘微循环从母体获取氧气和营养物质。胎盘是一个独特的器官，其自身发育并分化，并在整个妊娠过程中组织胎儿生长和母体状况。妊娠期间的几种危及生命的疾病，如妊娠高血压（PIH）和子痫，与胎盘功能障碍密切相关。为了解PIH的病理生理学，人们对遗传易感性和胎盘形成不良进行了深入研究。目前认为，“胎盘形成不良假说”，即绒毛外滋养层细胞未能充分侵入胎盘床，部分解释了母体患此病的易感性。累积研究表明，胎儿胎盘部位的缺氧微环境、子宫胎盘血流的剪切应力以及异常分泌到母体循环中的促炎物质协同促进了PIH的进展。例如，PIH母亲循环中血管内皮生长因子受体-1（sVEGFR-1）的可溶性形式和CD105的可溶性形式升高。然而，随着母体全身疾病的恶化，妊娠后半期胎盘的病理事件仍知之甚少。为了更好地理解PIH并采取有效的治疗方法，阐明PIH相关胎盘变化的病理过程很重要。在这篇综述中，总结了目前对胎盘发育和PIH胎盘病理生理学的认识。此外，还讨论了PIH和啮齿动物PIH模型中血管活性信号的最新发现。
