The Role of Estrogen Receptor-Beta on Human Fetoplacental Vasculature

描述（由申请人提供）：胎儿胎盘循环是胎儿正常生长和发育的关键组成部分。该血管系统内的异常血流通常与胎儿生长受限相关，如脐动脉和静脉多普勒指数所示。这些变化增加了死产的风险，为了避免这种结果，通常需要早产。此外，生长受限的早产儿往往表现出更严重的早产表现比他们的年龄匹配，适当增长的同行。生长受限的长期后果同样令人担忧，有强有力的证据表明成年后心血管疾病、代谢综合征和肥胖的风险增加。我们的长期研究目标是确定导致胎盘内皮细胞功能障碍的分子机制（即，胎儿胎盘血管内衬的细胞）。这些研究将在主要导师（塞尔达尔布伦博士）的实验室进行，其他导师、合作者和顾问（道格拉斯洛索尔多博士、罗纳德马格内斯博士、琳达恩斯特博士）将提供意见。本研究培训计划的目标是建立成为独立研究者的能力。总的来说，我们预计这些研究将有助于更好地了解在胎儿生长受限的情况下这些血管内发生的变化，并有望为未来的预防和治疗提供目标。

DESCRIPTION (provided by applicant): The fetoplacental circulation is a critical component to normal fetal growth and development. Abnormal blood flow within this vascular system is often found in conjunction with fetal growth restriction as demonstrated by umbilical artery and vein Doppler indices. These changes increase risk for stillbirth, and preterm delivery is often warranted in order to avoid this outcome. Furthermore, preterm neonates with growth restriction tend to demonstrate more severe manifestations of prematurity than their age-matched, appropriately-grown counterparts. Long- term consequences of growth restriction are just as concerning, with strong evidence of increased risks for cardiovascular disease, metabolic syndrome, and obesity in adulthood. Our long-term research goal is to determine the molecular mechanisms responsible for dysfunction of placental endothelial cells (i.e., the cells lining the fetoplacental vessels) in pregnancies complicated by fetal growth restriction. These studies will be performed in the primary mentor's (Dr. Serdar Bulun) laboratory, with the input of other mentors, collaborators, and consultants (Dr. Douglas Losordo, Dr. Ronald Magness, Dr. Linda Ernst). The goal of this research training plan is to establish the ability to become an independent investigator. In total, we anticipate that these studies will contribute critical knowledge in better understanding the changes that occur within these vessels in the setting of fetal growth restriction and hopefully provide targets for prevention and therapy in the future.