A gene regulatory network or genetic regulatory network is a collection of DNA segments in a cell which interact with each other indirectly (through their RNA and protein expression products) and with other substances in the cell, thereby governing the expression levels of mRNA and proteins. In general, each mRNA molecule goes on to make a specific protein (or set of proteins). Genetic differences in the ability to regulate iron in the placenta tissue are likely to contribute; however, identifying the underlying genes is difficult. Placenta iron regulation is highly complex, involving many genes and biochemical pathways. These genes act at multiple levels, e. g., transcriptionally and post-transcriptionally, and by different mechanisms, e. g. transport, absorption, storage, and export. Moreover, they may interact with environmental factors such as diet. The aim of the study was to evaluate the expression of genes HIF1A, eNOS, VEGFA and PIGF, which form a gene regulatory network in the placenta of pregnant women with signs of iron deficiency anemia. Material & Methods. The research was performed at the maternity hospital № 2 (Odessa) and Genetic Laboratories “Nadiya” (Kyiv). The study involved 150 women in labor and placenta samples were obtained from them. Thus were the following clinical groups: I group – the placenta samples of women with physiological pregnancy and childbirth (n = 30). The second group – the placenta samples of pregnant women with a history of anemia (n = 40). The third group – the placenta samples of women with placental dysfunction and a history of anemia (n = 80). RNA analysis was conducted at the Clinic of Reproductive Medicine “Nadiya” from biopsy samples of placentas to investigate gene expression HIF1A (OMIM 603348), eNOS (OMIM 163729), VEGFA (OMIM 192240) and PIGF (OMIM 600153). For completing the analysis of gene expression there were consistently carried out the following procedures: sampling and biopsy of the placenta, the selection of RNA by the reverse transcription and polymerase chain reaction (PCR) in real time. Analysis of genetic networks was performed using the software GeneMania. Statistical analysis performed in the R environment. Results. In the analysis of gene network revealed that its membership includes genes that control the synthesis of hypoxia inducible protein (family of EGLN), metabolism of xenobiotics (ARNT, FLT, PLIN), placental growth factor (PGF), state of nitric oxide depending regulatory systems (NOSTRIN), energy supply functioning of body cells and so on. The most strong functional relationships were observed between genes HIF1A, eNOS and VEGFA. The analysis of gene network components determined that with iron deficiency anemia gene expression of HIF1A and VEGFA increased in 10. 2 and 10. 9 folds, while the presence of placental dysfunction increment expression is less pronounced, which may be due to the exhaustion of the adaptive capacity of the organism. Thus the changes in expression of genes involved in studied genetic networks indicate active adaptation during pregnancy to chronic hypoxia that accompanies iron deficiency. However, an isolated score expression of individual genes were apparently not essential to predict the needs of pregnancy and perinatal outcomes of clinical.
iron deficiency anemia, pregnancy, genetics, adaptation
«Bulletin of problems biology and medicine» Issue 4 part 1 (113), 2014 year, 117-120 pages, index UDK 618. 36 – 06 : 616. 155. 194] – 056. 7 – 07 – 08
