Grant: Project Grant

Preeclampsia is a major disorder of human pregnancy, characterized by high blood pressure and damage to organs. It is not only the leading cause of maternal death and stillbirth but also affects the health of mothers and children later in their lives. It is believed that preeclampsia is a two-stage disorder. In the first stage, defective placental development, particularly insufficient transformation of uterine spiral arteries from high resistant, low flow blood vessels into low resistant, high flow ones, results in reduced blood supplies from the mother to the placenta and the developing fetus. The second stage is the development of maternal symptoms mediated by the imbalanced release of pro- and anti-angiogenic factors from the stressed placenta. We have recently discovered that two protein isoforms derived from a gene named NLRC5 are expressed in the placenta and significantly upregulated in preeclamptic patients. Our preliminary results suggest that these NLRC5 isoforms play important roles in regulating placental development, and their upregulation contributes to the pathogenesis of preeclampsia. In this study, we will further investigate the role of these NLRC5 isoforms in the human placenta. We will also examine how they exert their functions in the placenta and use an animal model to determine if their overexpression will lead to the development of preeclampsia-like symptoms. The proposed study will provide novel insights into the function of NLRC5 isoforms in healthy and compromised pregnancies. It may ultimately result in the development of novel strategies for the prevention and treatment of preeclampsia and, consequently, improve the health and quality of life in pregnant women and infants.