Project 1. Preeclampsia dysregulates fetal endothelial responses to growth factors and cytokines
Preeclampsia (PE) is a hypertensive disorder that occurring in 3-8% of all human pregnancies. While PE is characterized by maternal endothelial dysfunction, little is known about PE-induced fetal endothelial dysfunction. However, PE children face increased risks of cardiovascular disorders (e.g., hypertension and stroke) later in life. Endothelial dysfunction is a hallmark of cardiovascular disease. We aims to define the sexual dimorphisms in PE-induced fetal endothelial dysfunction and dissect the underlying mechanisms, which will advance our understanding of PE-associated fetal endothelial dysfunction & adult-onset cardiovascular disease and ultimately lead to diagnostic and therapeutic strategies for cardiovascular risk prediction, treatment, and prevention in PE children.
Poject 2: Preeclampsia-Induced Fetal Endothelial Dysfunction in Obese Pregnancy
Preeclampsia (PE) is a hypertensive disorder and one of the leading causes of fetal/maternal morbidity and mortality during pregnancy. PE is characterized by impaired fetal and maternal endothelial function and excessive inflammation. Children born to PE will face increased risks of cardiovascular disorders later in life, suggesting that PE programs fetal vascular cells in utero. To date, the mechanisms underlying PE-associated fetal endothelial dysfunction remain elusive. Maternal obesity is one of the prevalent risk factors that associated with PE in developed countries. Maternal obesity increases the overall risk of PE by 3 fold. Children born to obese mother also exhibit higher blood pressure and increased risks of adverse cardiovascular outcomes in adulthood. We aim to elucidate the roles of miRNAs in PE-induced fetal sex- specific endothelial dysfunction in lean and obese pregnancies. In the long term, these studies may reveal novel biomarkers or therapeutic targets for fetal sex-specific cardiovascular risk prediction, treatment, and even prevention in children born to lean and obese PE.
Poject 3: Effect of maternal DBP exposure on Fetal-placental endothelial function during pregnancy
Fetal vascular/endothelial dysfunction during pregnancy has long-term adverse effects on the cardiovascular health of the offspring. Phthalates are a group of environmental endocrine disruptors that widely exist in the environment and adversely impact cardiovascular function.
Dibutyl phthalate (DBP) is a phthalate congener associated with adverse pregnancy/fetal outcomes (e.g, fetal growth restriction) and cardiovascular diseases in the offspring, which is indicative of in-utero programming of the fetal vascular/endothelial function. Women of reproductive age have a significant burden of DBP exposure through consumer products, occupational exposure, and medication. Higher urinary DBP metabolite levels (indicative of higher exposure) were observed in Hispanic and non-Hispanic black women than in other ethnic groups. Biomonitoring studies reported positive DBP exposure in most mothers and babies during pregnancy. To date, the effect of prenatal DBP exposure on fetal placental vascular/endothelial development and function is unclear. In this study, we will examine the cellular and molecular mechanisms underlying the adverse effects of DBP exposure during pregnancy on fetal vascular development and function. Results from this study will provide important information on how phthalates exposure affects placental function as well as the fetal-sex specific programming of fetal vascular/endothelial development and function.