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.
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| 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 |
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| 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 |
| Sween, Lindsay K; Althouse, Andrew D; Roberts, James M (2015) Early-pregnancy percent body fat in relation to preeclampsia risk in obese women. Am J Obstet Gynecol 212:84.e1-7 |
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