Placental genotype /phenotype: PE /other complications

Magee-Women'S Res Inst And Foundation, Pittsburgh PA

Investigators

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Abstract

Many pregnancy complications are associated with specific placental pathologies. Our research has focused on the placenta in preeclampsia (PE), a syndrome that alters maternal vascular function and restricts intrauterine fetal growth (IUGR). In PE, cytotrophoblast (CTP) invasion of the uterus and its vessels is often rudimentary. The consequent reduction in maternal blood flow to the placenta is thought to be an important part of the syndrome's lesions found in PE occur in other pregnancy complications. We recently confirmed that IUGR is sometimes associated with shallow CTB invasion and discovered a similar lesion in patients with chorioamnionitis who give birth prematurely. If other pregnancy complications are also associated with shallow CTB invasion, what are the molecular levels. We now propose a comparison of tissue samples of the fetal maternal interface obtained from the three patient groups in which we observe shallow placentation: women with PE, women without PE who give birth to infants who are small for gestational age, and women with chorioamnionitis who deliver prematurely. The control samples matched for gestational age, will be obtained from patients with clinically normal pregnancies and with pregnancy complications in which we find CTB invasion is morphologically normal. The latter group includes women who deliver prematurely for reasons other than chorioamnionitis. The Specific Aims are as follows: First, we will assess the contribution of genetic anomalies. The techniques to be used include fluorescent in situ hybridization and comparative genomic hybridization. Second, we will investigate the rate of apoptosis, before examining the state of CTB differentiation in relationship to hypoxia and expression of molecules with potentially important immune functions by using immunolocalization and in situ hybridization techniques. At the conclusion of these experiments we will have assembled a set of genetic and molecular markers that differentiate the placental lesions that occur in PE from those associated with other pregnancy complications. This information will provide valuable insights into the etiology of PE. In addition, the studies of placental aneuploidy provide an exciting opportunity to correlate genotype with phenotype, an experimental strategy that has yielded a wealth of data in other experimental systems, from yeast to mice.