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）的重要临床问题。超声和多普勒超声评估的FGR和PE的存在与否将代表自变量，细胞和分子生物学技术将代表因变量。现有的关于PPARg活性的数据强烈表明，在PPARg -/-小鼠中，胎盘缺乏PPARg是滋养细胞分化和功能严重破坏的基础。重要的是，最近的证据发现p38a是小鼠和人类滋养层细胞中PPARg活性的重要上调因子，具有特异性的p38ct抑制剂，导致PPARg活性和滋养层细胞分化显著降低。我们假设在FGR和PE患儿的异常胎盘中存在p38ct和PPARg基因表达水平的异常。本研究的目的是将以往正常足月胎盘的研究结果扩展到远足月分娩（对照组）和FGR和PE合并妊娠（研究组）的胎盘，进一步研究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.