Genome-Wide Analysis in the Study of the Fetal Growth Restriction Pathogenetics

Abstract—Fetal growth restriction is a complication of pregnancy that is defined as the inability of the fetus to realize its genetically determined growth potential. Despite the high social and medical significance of this problem the exact pathogenesis of fetal growth restriction is not known. Therefore, the analysis of the molecular genetics mechanisms of this pathology within the framework of approaches using modern high-performance technologies of next generation sequencing is of undoubted interest. In this review we focused on the analysis of data obtained in studies of the genetics component of fetal growth restriction. The authors of these studies used next generation sequencing technologies and carried out whole transcriptome profiling. The results of the gene expression genome-wide analysis in placental tissue allow us to identify 1430 differentially expressed genes between fetal growth restriction and normal pregnancy, of which only 1% were found in at least two studies. These differentially expressed genes are involved in the Wnt/β-catenin signaling pathway, which plays an important role in cell migration, neural pattern formation and organogenesis during embryonic development. Common genes are associated with both obstetric and gynecological diseases, as well as with various somatic conditions from the groups of neurodegenerative, cardiovascular diseases and mental disorders, which probably reflects their involvement in the development of postnatal consequences of fetal growth restriction. The results of our work do not only point to potential molecular mechanisms and key genes underlying fetal growth restriction, but also indicate the important role of gene–gene communications in this pathology: about 30% of all identified differentially expressed genes products interact with each other within the same gene network. In general, genome-wide RNA sequencing combined with the analysis of protein–protein interactions represents a promising direction in research in the development and functioning of the placenta, as well as the identification of genetic mechanisms of placental insufficiency diseases, including fetal growth restriction.