The placenta is a transient organ with remarkable functions. Differentiation of its specialized epithelial cells,termed cytotrophoblasts (CTBs), is an important determinant of both its form and function. Our focus is thepathway that gives rise to the invasive subpopulation of cells. During interstitial invasion, a subset of CTBscommingles with resident decidual and immune cells. During endovascular invasion, these fetal cells invadethe maternal blood vessels, which they subsequently line. Together, these two components of CTB invasionanchor the placenta to the uterus and divert uterine blood flow to the intervillous space. Given thecomplexities involved in this explosive process, it is not surprising that anomalies sometimes occur.Preeclampsia (PE), a syndrome that adversely affects the mother (by altering vascular function) and thefetus (by restricting intrauterine growth), is a prime example. Interstitial and endovascular invasion is shallow,and fewer spiral arteries are modified in toto. Our long-term goal is to elucidate the molecular bases of theplacental defects that occur in PE and to explain their relationship to the clinical signs of this syndrome.Previously, we showed that in normal pregnancy CTB invasion is accompanied by a phenotypic switch inwhich these ectodermal derivatives take on many characteristics of endothelial cells. PE is associated withspecific deficits in this program as evidenced by defects in adhesion molecule switching and perturbations intheir production of angiogenic substances. Recently, we used an unbiased microarray approach to identifynovel pathways that function within the basal plate region where the placenta attaches to the decidua. First,we studied the effects of advancing gestational age on gene expression in this area and then we examinedthe impact of PE. The results of these experiments revealed a wealth of new information. For example,consistent with the hypotheses to be tested in this program project, lipid pathways are among the mosthighly modulated in both analyses. In addition, molecules with known patterns of regulation (e.g., CRH innormal pregnancy; leptin and sFlt-1 in PE), were expressed in the expected manner, data that strengthen theimportance of our novel findings. Accordingly, we now propose using a microarray approach to analyze theeffects of PE on CTB invasion. Specifically, we will isolate the progenitors from affected and controlplacentas and compare their patterns of gene expression as they differentiate/invade in vitro (Aim 1). Thenwe will determine the functional significance of the changes we observe (Aim 2). We think that theseexperiments will yield fundamental new insights into the basic placental defects that lead to PE. Additionally',the results could also have clinical utility in prediction and/or diagnosis of this pregnancy complication, withthe identification of potential therapeutic targets another possibility.
| Global Pregnancy Collaboration:; Schalekamp-Timmermans, Sarah; Arends, Lidia R et al. (2017) Fetal sex-specific differences in gestational age at delivery in pre-eclampsia: a meta-analysis. Int J Epidemiol 46:632-642 |
| Hux, Vanessa J; Roberts, James M; Okun, Michele L (2017) Allostatic load in early pregnancy is associated with poor sleep quality. Sleep Med 33:85-90 |
| Countouris, Malamo E; Schwarz, Eleanor B; Rossiter, Brianna C et al. (2016) Effects of lactation on postpartum blood pressure among women with gestational hypertension and preeclampsia. Am J Obstet Gynecol 215:241.e1-8 |
| Gandley, Robin E; Althouse, Andrew; Jeyabalan, Arundhathi et al. (2016) Low Soluble Syndecan-1 Precedes Preeclampsia. PLoS One 11:e0157608 |
| Schmella, Mandy J; Clifton, Rebecca G; Althouse, Andrew D et al. (2015) Uric Acid Determination in Gestational Hypertension: Is it as Effective a Delineator of Risk as Proteinuria in High-Risk Women? Reprod Sci 22:1212-9 |
| Luiza, John W; Gallaher, Marcia J; Powers, Robert W (2015) Urinary cortisol and depression in early pregnancy: role of adiposity and race. BMC Pregnancy Childbirth 15:30 |
| Hux, Vanessa J; Roberts, James M (2015) A potential role for allostatic load in preeclampsia. Matern Child Health J 19:591-7 |
| Hassis, Maria E; Niles, Richard K; Braten, Miles N et al. (2015) Evaluating the effects of preanalytical variables on the stability of the human plasma proteome. Anal Biochem 478:14-22 |
| Catov, Janet M; Abatemarco, Diane; Althouse, Andrew et al. (2015) Patterns of gestational weight gain related to fetal growth among women with overweight and obesity. Obesity (Silver Spring) 23:1071-8 |
| Founds, Sandra A; Ren, Dianxu; Roberts, James M et al. (2015) Follistatin-like 3 across gestation in preeclampsia and uncomplicated pregnancies among lean and obese women. Reprod Sci 22:402-9 |
Showing the most recent 10 out of 249 publications
