Плацента - специфический и важнейший орган при беременности, состоящий из клеток трофобласта от внеэмбрионального слоя бластоцисты. Она выполняет ряд функций, направленных на поддержание роста и развития плода, включая регулировку температуры, защиту от инфекций, обеспечение иммунологической толерантности к плоду, обеспечение газообмена и транспорта питательных веществ, продуктов жизнедеятельности и многие другие функции. Правильное развитие плаценты необходимо для успешного вынашивания беременности. Отклонения от нормального пути роста и функционирования приводят к различным осложнениям, таким как плацентарная недостаточность, задержка внутриутробного развития плода, преэклампсия, преждевременные роды. Причины дисфункции плаценты изучаются многие десятилетия, однако до сих пор существуют контроверсии в мнениях касательно механизмов развития и маркеров диагностики нарушений в фетоплацентарном комплексе. Частично это обусловлено сложностью доступа к плаценте, так как фактически исследовать ее представляется возможным только после рождения плода, что может делать картину изменений нечеткой. Однако развитие технологий, лабораторных и инструментальных методов исследований неутомимо прогрессирует, что позволяет нам каждый раз раскрывать новые механизмы и лучше понимать цепочку нарушений внутриплацентарных процессов. В настоящее время ученые всего мира уделяют особое внимание внутриклеточным «событиям», среди которых основными являются воспаление, апоптоз и определенные моменты иммунного ответа организма беременной женщины. Эти механизмы с одной стороны являются абсолютно разными, однако существующие сигнальные пути, благодаря которым происходит кооперация различных молекулярных процессов, часто сходятся на каких-либо звеньях патогенеза, усиливая или уменьшая свое действие. Такую же характеристику можно дать двум биологически активным субстанциям - р-65-субъединице транскрипционного фактора NF-κB и каспазы-3, которые постепенно обращают на себя внимание в качестве маркеров развития патологии в плаценте. Если каспазы отображают активность только механизма апоптоза, то NF-κB является очень сложным белковым фактором, разные субъединицы которого способны регулировать разные процессы: воспаление, иммунный ответ и даже апоптоз. Нарушение в регуляции или пороговой активности данного комплекса приводит к развитию различных отклонений в функции плаценты, приводя к плацентарной недостаточности. Дополнительно стоит отметить, что в последнее время обращает на себя внимание васкулярный эндотелиальный ростовой фактор VEGF, который склонен к развитию полиморфизмов за счет наличия нескольких интронных и экзонных областей. Это, как следствие, часто может приводить к так называемым SNP - заменам одного нуклеотида другим, дефектам в структуре и функционировании всего белка ростового фактора. Это негативно влияет на ангиогенез и развитие плацентарной площадки, что также приводит к недостаточности «детского места», что может быть причиной развития преждевременных родов и задержки внутриутробного развития плода. Таким образом, данная статья представляет собой обзор литературы, речь в котором пойдет о новых механизмах развития плацентарной недостаточности и роли вышеупомянутых факторов в возникновении дисфункции плаценты, а также сопровождающих ее акушерских осложнений, в частности - преждевременных родов. The placenta is a specific and most important organ during pregnancy, consisting of trophoblast cells that arise from the extraembryonic layer of the blastocyst. It performs a number of functions aimed to support the growth and development of the fetus, which include temperature regulation, anti- infectious protection, providing immunological tolerance to the fetus, gas exchange and transport of nutrients, waste products, and many other functions. Proper development of the placenta is essential for successful gestation. Deviations from the normal path of growth and functioning lead to various complications, such as placental insufficiency, intrauterine growth restriction, preeclampsia, and premature birth. The causes of placental dysfunction have been studied for many decades, but there are still controversies in opinions regarding the mechanisms of development and markers for the diagnosis of disorders in the fetoplacental complex. This is partly due to the difficulty of accessing the placenta, since in fact it is possible to examine it only after the birth of the fetus, which can make the picture of changes unclear. However, the development of technologies, laboratory and instrumental research methods progresses, which allows us to discover new mechanisms and understand better the chain of defects in intraplacental processes. Currently, scientists around the world are paying special attention to intracellular “events”, among which the main ones are inflammation, apoptosis and certain moments of the immune response of the body of a pregnant woman. On the one hand, these three mechanisms are completely different, however, the existing signaling pathways, due to which the cooperation of various molecular processes occurs, often converge on some points of pathogenesis, increasing or decreasing the summary action. The same characteristic can be given to such biologically active substances as p-65- subunit of the transcription factor NF-κB and caspase-3, which are gradually attracting attention as markers of the development of pathology in the placenta. If caspases display the activity of apoptosis mechanism only, NF-κB is a very complex protein factor, different subunits of which are capable of regulating different processes: inflammation, immune response and even apoptosis. A disturbance in the regulation or threshold activity of this complex leads to the development of various abnormalities in the function of the placenta, leading to placental insufficiency. Additionally, it should be noted that scientists all over the world payed an attention to the vascular endothelial growth factor VEGF, which is prone to the development of polymorphisms due to the presence of several intron and exon regions. As a consequence, this can often lead to the so-called SNP - the replacement of one nucleotide with another, that results in a defect in the structure and functioning of the entire growth factor protein. This negatively affects angiogenesis and the development of the placental site, that also leads to a lack of «baby seat» functioning, which can be the cause of the development of premature birth and intrauterine growth retardation of the fetus. Thus, this article is a literature review, that focuses on new mechanisms for the development of placental insufficiency and the role of the above mentioned factors in the occurrence of placental dysfunction and the accompanying obstetric complications, particularly - preterm labor.

Objective: to study the hemostatic efficacy of compression of the lower uterine segment (COLUS) as a new method to stopping bleeding during cesarean section on the background of placenta previa.Materials and methods. The main group included 30 women with placenta previa, who were routinely delivered by cesarean section and using the COLUS technique after separation and isolation of placenta during a gestation period of 36 weeks – 36 weeks + 6 days. The control group consisted of 31 pregnant women with placenta previa, who had a planned delivery by сesarean section using the classical technique of suturing the uterus at a gestational age of 38–39 weeks. After separation and isolation of the placenta placental bleeding was stopped by flashing and coagulation of bleeding vessels in lower uterine segment.Results. In the control group after standard caesarean section technique a high percentage of blood loss from 1000 ml or more was observed, that is typical for operations performed with placenta previa. In the main group a significantly smaller number of cases of blood loss from 1000 ml or more were observed. The average volume of blood loss in the control group was 1277 ± 119 ml, and 697 ± 139 ml in the main group, that is indicates the high efficiency of the COLUS technique. This technique allows to reduce blood loss by 45% of the blood loss of the control group. There was no significant difference in the condition of the newborns in both groups.Conclusions. The data obtained indicate the advisability of delivery of pregnant women with placenta previa in the gestation period of 36 weeks – 36 weeks + 6 days. Performing a cesarean section in the absence of a developed lower uterine segment in combination with the COLUS technique is an effective and safe surgical method for prevention of blood loss in a complex of therapeutic measures to prevent massive obstetric bleeding. It is an addition to surgical means to stop bleeding from the lower uterine segment after separation and removal of the underlying placenta

Objectives: to study the levels of the total, phosphorylated p65-subunit of the nuclear factor NF-kB, activity of p65 and the relation with the level and ratio of T-helpers type I and II in pregnant women with placental dysfunction and different clinical types of the course of preterm labor (with preterm premature rupture of membranes (pPROM) and without it).Materials and methods. The case-control study included 60 pregnant women: 40 women with placental disorders and spontaneous premature labor in the period of 24–34 weeks (group I – 20 women with premature labor and timely discharge of amniotic fluid, group II – 20 women with pPROM) and 20 women of the control group (CG) with normal timely delivery in the head position of a fetus without complications.The value of the total NF-kB p65 subunit and its phosphorylated fraction was determined in all women using ELISA in placenta lysates. On this basis the p65 subunit activity was calculated; number of T-helper I (Th1) and T-helper II (Th2) was determined using flow cytometry in a whole blood sample, with afterward calculation of the Th1/Th2 ratio.Results. Elevated levels of total p65 and its phosphorylated fraction were found in women with placental dysfunction (p < 0.01 in groups I and II compared with CG), as well as the activity p65 (p < 0.01 in group I, p = 0.04 in group II compared with CG). The difference in the Th1 value and the Th1/Th2 ratio was significantly higher in both groups (p < 0.01 in group I, p = 0.03 in group II for Th1; p < 0.01 in both groups for Th1/Th2), the number of Th2 differed significantly only in group I (p < 0.01 compared with CG). A strong positive correlation between p65 activity and Th1/Th2 was also established (r = 0.8).Conclusions. Obtained data indicates the increased NF-kB p65-subunit activity in women with placental disorders and spontaneous premature labor without pPROM, which is impact on the increase of the Th1/Th2 ratio due to the Th1 increase. This mechanism might be considered to be the leading cause of the premature birth in this group of pregnant women. However, for women with the preterm labor activity with pPROM, the difference with GC has a lower level of significance, which may indicate the existence of another leading mechanism for the initiation of premature labor in this group.

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.

The objective: study of histochemical, morpho-functional features of placentas in premterm birth at different gestational ages. Materials and methods. We examined 172 pregnant women, who were hospitalized and gave birth in the Perinatal Center of Kyiv during 2016–2018 years at 24–33 weeks of gestation. The control group included 40 women with a physiological course of singleton pregnancy at 38–41 weeks of gestation. Patients of the experimental group were divided into three subgroups: the first consisted of 46 pregnant women at 22–27 weeks of gestation, the second one – of 44 pregnant women at 28–33 weeks, the third one – of 42 pregnant women at 34–37 weeks. Clinical and statistical analysis of exchange cards of pregnant women (form 113/y) and birth histories (form 096/0) of mothers of all groups was performed. For morphofunctional assessment of placenta in the study histological (staining with hematoxylin-eosin after Van-Gizon) and immunohistochemical (indirect streptavidin-peroxidase – for detection of progesterone receptor’s expression level) methods were used. Results. No significant age difference was found between the study groups. More than 66.5% of patients had a second pregnancy. Obstetric and gynecological history of women are burdened in most cases by the following conditions: previous premature birth, miscarriage, inflammatory diseases, extragenital pathology (diseases of the urinary and endocrine systems). When analyzing the results of histological examination of the placenta in patients whose pregnancies resulted in childbirth at 22–27 weeks, inflammatory changes in the placenta were found in 84.8%, and in women in labor at 28–33 weeks – only 56.8%. At 34–37 weeks of gestation, the percentage of inflammatory changes in placental structures do not have a significant difference with the control group (30.9% and 27.5%, respectively; p≤0.05). With gestational age increase the percentage of involutive-dystrophic changes in the placenta decreases, the number of circulatory disorders increases, and accelerated chorionic maturation is observed. Analysis of the data of monoclonal antibodies’ to progesterone receptors expression in the structures of the placenta depending on gestational age revealed the greatest expression in decidual membranes (55%) in very early preterm birth, which had a significant difference with the control group (14%), (p<0.05) . In women of group II, the level of expression of progesterone receptors was reduced (30%), but had no significant difference with group III of the studied placentas (26%), (p>0.05). Immunohistochemical examination of the progesterone receptors (PR) shows a reaction in the epithelium and stem cells of the stroma, intermediate and terminal villi; in amniotic membranes and extravillous cytotrophoblast; in the vascular endothelium. Conclusion. In very early preterm birth, inflammatory changes and significant expression activity of progesterone receptors predominate in placental structures. During childbirth at 33–37 weeks of gestation the most common disorders are maturation of the villous chorion, combined with circulatory and involutive-dystrophic changes. Keywords: preterm labor, placenta, histological changes, immunohistochemistry, progesterone receptors.