Project 3

The human placenta is a unique temporal organ that originates from the trophectoderm of the blastocyst and develops into a complex functionally active structure that mediates the tight interactions between the fetus and the maternal organism. During the whole period of gestation placenta undergoes molecular, structural and functional rearrangements to meet the requirements of fetal and maternal organisms. The abnormalities in placental functions lead to the health problems for mother and child during gestation and after it. The syndrome of preeclampsia is one of the major complications of pregnancy (7 – 10% worldwide) and the leading cause of maternal and fetal morbidity and mortality. While the exact cause of preeclampsia remains unclear, there is strong evidence that a major cause predisposing a susceptible woman to preeclampsia is an abnormally implanted placenta yielding a state of hypoxia and increased oxidative stress, the release of anti-angiogenic proteins along with inflammatory mediators into the maternal plasma and generalized endothelial dysfunction.

We focus our research on two apsects - folate-related one-carbon unit metabolism as a basic metabolic systems in the cell and placental transcriptome during placental development in health and preeclampsia. The folate-related one-carbon unit metabolism is responsible for de novo biosynthesis of nucleic acid precursors, purines and pyrimidines, methionine and S-adenosylmethionine hence for the basic cellular processes as proliferation, differentiation, epigenetic regulation of gene expression, energy conservation and transport, co-enzymes synthesis, signal transduction and translation. Gene expression profiling provides the most global possible picture and the basis for inferring gene regulatory network. Analysis of the transcriptome of human placenta is used to understand the molecular mechanisms and signaling pathways controlling placenta development in health and preeclampsia.