Effect of Leptin on Trophoblast Invasiveness

描述（由申请人提供）：我打算研究瘦素和滋养细胞侵袭之间的关系。在妊娠早期，胚胎滋养层细胞对子宫上皮的侵入对于胎盘的建立和发育至关重要，而胎盘的建立和发育又是胎儿健康发育所必需的。瘦素是一种由脂肪组织产生的激素，在某些物种中，胎盘作为生殖系统营养状态的信号。拟议的项目将试图描述营养影响胎盘发育的机制之一，并增加我们对瘦素在先兆子痫中的作用的理解，先兆子痫是一种常见的妊娠并发症，其特征是滋养层浸润不足。妊娠早期和晚期滋养层细胞侵袭性的差异将用于研究瘦素的作用。我将使用原代小鼠滋养层细胞来检验以下假设：（1）瘦素促进胎盘细胞中滋养层细胞从妊娠早期侵入，而不是晚期侵入;（2）这种侵入是由MMP活性的增加介导的，MMP活性是（3）通过MAPK信号通路刺激的。

DESCRIPTION (provided by applicant): I propose to investigate the relationship between leptin and trophobiast invasion. Invasion of the uterine epithelium by embryonic trophoblast ceils during early pregnancy is crucial for the establishment and development of the placenta, which is in turn necessary for healthy fetal development. Leptin is a hormone produced by adipose tissue, and in some species, the placenta, that acts as a signal of nutritional state to the reproductive system. The proposed project will attempt to characterize one of the mechanisms by which nutrition affects placental development, and increase our understanding of the role of leptin in pre-eclampsia, a common complication of pregnancy characterized by insufficient trophoblast invasion. The difference in invasivness between trophoblast ceils from early and late pregnancy will be used to study the effects of leptin. I will use primary mouse trophoblast ceils to test the hypotheses (1) that leptin promotes trophoblast invasion in placental ceils from early, but not late pregnancy and (2) that this invasion is mediated by an increase in MMP activity, which is (3) stimulated via the MAPK signaling pathway.