Role of p65 NF-κB, caspase-3 activities and VEGF gene polymorphisms on the development of preterm labor in women with placental dysfunction

Abstract

The objective: to study the activity of the p65 subunit of the nuclear factor – NF-κB and effector caspase-3, as well as the presence of a single nucleotide polymorphism of the VEGF gene (936C/T) in pregnant women with placental disorders and various clinical types of the course of premature labor (with premature rupture of the membranes and without it).Materials and methods. At the clinical base of the Department of Obstetrics and Gynecology No. 1 of O. O. Bogomolets National Medical University, which is located in the non-commercial enterprise “Perinatal Center of Kyiv”, during 2019–2022, a case-control study was conducted with the involvement of 90 pregnant women: 60 women of the main group with placental disorders and the development of spontaneous premature labor in the period of 24–34 weeks of gestation (I group – 30 women with premature labor and premature rupture of membranes, II group – 30 women with premature rupture of the membranes) and 30 women of control group (CG) with term normal delivery and the physiological course of the pregnancy.In pregnant women, the number of total and activated fractions of the p65 subunit of nuclear factor NF-κB and caspase-3 was determined by enzyme-linked immunosorbent assay (ELISA) in placenta lysates with further calculation of their activity based on these data, as well as the presence of a single nucleotide polymorphism of the VEGF gene (936C/T) using the polymerase chain reaction.Results. In women with placental disorders and preterm birth a significantly higher values of fraction content and activity of p65 NF-κB and caspase-3 were found, with some peculiarities within the groups compared to the control group. Women of the I group were characterized by a higher activity of p65-subunit of nuclear factor (I group — 61.6 % with 95 % CI 59.7–64.2; II group — 33.8 pg/ml with 95 % CI 31.2-35.2; CG — 27.3 pg/ml, 95 % CI 26.4–28.6; p<0.05). Pregnant women of the II group had higher values of caspase-3 activity (II group — 59.2 % with 95 % CI 57.4–59.8, I group — 39.5 % with 95 % CI 38.5–40.5, CG — 31.2 %, 95 % CI 30.4–31.9; p<0.01). It was established that the presence of the T allele at position 936 of VEGF gene polymorphism is a risk factor for the development of placental disorders with the development of premature labor, the rate of this allele in the main group was 11.7 % versus 1.7 % – in the control cohort (p<0.05).Conclusions. Pregnant women with placental disorders and the development of premature birth are characterized by an increased activity of the p65 subunit of nuclear factor κB and caspase-3 compared to the control group: in women without premature rupture of the fetal membranes, a significant 2.2-fold increase in p65 NF-κB activity was found, and caspase-3 activity – by 1.3 times; in the group of pregnant women with preterm premature rupture of membranes the level of caspase-3 activity exceeded the control group by 1.9 times, and the level of p65-subunit of nuclear factor activity — by 1.2 times (p<0.01 for all groups).936(C/T) single nucleotide polymorphism of the vascular endothelial growth factor gene was determined significantly more often in women with placental disorders and preterm birth (11.7 % in the study group versus 1.7 % in CG, p<0.05), the T-allele on the VEGF gene carriers may be associated with the development of these pregnancy complications. However, a study on a larger sample of women is needed to obtain definitive results.