Die Rolle der PPARy Zielgene und der Zell-Zellfusion von Zytotrophoblasten in normalen und pathologischen Plazenten, wie Preeklamspie, HELLP-Syndrom und fötaler Wachstumsrestriktion.

该提案解决了胎儿生长受限(FGR)和子痫前期(PE)这两个重要的临床问题。通过超声和多普勒超声评估FGR和PE的存在或不存在将代表自变量，细胞和分子生物学技术代表因变量。关于PPARg活性的现有数据有力地表明，胎盘PPARg的缺乏是PPARg-/-小鼠滋养层细胞分化和功能严重中断的基础。重要的是，最近的证据发现，在小鼠和人滋养层细胞中，P38A是PPARg活性的重要上调因子，而特定的P38ct抑制剂会导致PPARg活性显著降低和滋养层细胞分化。我们推测在FGR和PE患儿的异常胎盘中存在P38ct和PPARg基因的异常表达水平。本研究的目的是将以前在正常足月胎盘中发现的结果推广到远足分娩的胎盘(对照组)和合并FGR和PE的胎盘(研究组)，以进一步探讨PPARg和P38ot在胎盘发育中的作用。

The proposal addresses the important clinical problem of fetal growth restriction (FGR) and preeclampsia (PE). Presence or absence of FGR and PE as assessed by ultrasound and Doppler sonography will represent the independent variable, techniques in cellular and molecular biology the dependent variable. The data available on PPARg activity strongly suggest that the lack of placental PPARg underlies the profound disruption of trophoblast differentiation and fimction in PPARg -/- mice. Importantly, recent evidence has found p38a to be an important up-regulator of PPARg activity in murine and human trophoblasts with specific p38ct inhibitors leading to a marked decrease of PPARg activity and trophoblast differentiation. We hypothesize that aberrent gene expression levels of both p38ct and PPARg exist in abnormal placentas from babies with FGR and PE. The study aim is to extend previous findings in normal term placentas to placentas from pregnancies delivered remote from term (control group) and complicated by FGR and PE (study group) to further examine the role of PPARg and p38ot in placental development.