Decidual Membrane Research Articles

Clinical and morphological features of the myometrium in patients with placental adherent and invasive pathology

BACKGROUND: The fast increase in the frequency of placental adherent and invasive pathology worldwide accounts for the growing interest in studying the pathogenesis of placenta accreta. According to the literature, the clinical and morphological features of the myometrium from the placental attachment area in placental adherent and invasive pathology are described in single articles. Study of morphological features using proteolytic markers in the myometrium from the placenta accreta area could help in understanding the pathogenesis of placental adherent and invasive pathology. For the first time in this study, the clinical and morphological features of the myometrium from the placental attachment area in patients with uterine scar and placental adherent and invasive pathology are compared with the myometrium of women with uterine scar without placenta accreta and intact myometrium. AIM: The aim of this study was to evaluate the expression of matrix metalloproteinase 2 and tissue inhibitors of matrix metalloproteinases 1 and 2 in myometrial biopsies in placental adherent and invasive pathology. MATERIALS AND METHODS: This study included 15 myometrial biopsies from the placental site, which were divided into three groups according to the clinical diagnosis of the patients: group 1 (main group), with a uterine scar after cesarean section and placental adherent and invasive pathology (n = 5); group 2 (comparison group), with a uterine scar after cesarean section (n = 5); group 3 (control group), with a normal pregnancy without a uterine scar (n = 5). Histological examination was carried out using the standard procedure. Immunohistochemical study was performed using antibodies to matrix metalloproteinase 2 and tissue inhibitors of matrix metalloproteinases 1 and 2 (Abcam, USA). Morphometry was carried out using the VideoTesT-Morphology 5.2 program (Videotest Ltd., Russia). The statistical analysis was performed using the IBM SPSS Statistics 26.0 software. RESULTS: In the biopsies of the main group, we verified terminal chorionic villi with hypervascularization and uneven plethora of the vascular bed among hypertrophied muscle fibers, a basal plate with lumen ectasia of unevenly full-blooded vessels, and the absence of a decidual membrane, in contrast to groups 2 and 3. The matrix metalloproteinase 2 expression area in the main group was higher than in the comparison and control groups (p = 0.008; p1–2 = 0.049*, p1–3 = 0.011), the matrix metalloproteinase 2 optical density not differing between the groups (p = 0.122). The tissue inhibitors of matrix metalloproteinases 1 expression area was higher in the comparison group compared to the main group (p = 0.035; p2–3 = 0.032), and the tissue inhibitors of matrix metalloproteinases 1 and 2 optical density was higher in the comparison group compared to control (p = 0.008; p2–3 = 0.005). CONCLUSIONS: In myometrial biopsies of patients with a uterine scar and placental adherent and invasive pathology, we verified pathology of the basal plate of the placenta, increased matrix metalloproteinase 2 expression and decreased tissue inhibitors of matrix metalloproteinases 1 expression, which may indicate the peculiarities of the inflammatory response in the myometrium in placental adherent and invasive pathology.

The prevalence of inflammatory process in placentas from premature births in different gestational periods

Premature birth (PB) is the birth in less than 37 weeks, which can be spontaneous and iatrogenic, its frequency reaches 10% of all births. The pathogenesis of premature labor is based on the inflammatory reaction of the chorion, amnion and decidual membrane, but the origin of the inflammatory reaction is different depending on the gestational age.The objective: to study the prevalence of the inflammatory response in placenta samples from very early preterm, early preterm and term births.Materials and methods. Placenta samples from 203 parturient women who gave birth in the gestational period of 22–27 weeks – very early PB (I group – 101 parturient women with premature rupture of membranes (PROM), II group – 102 parturient women with the onset of labor with intact membranes) and 202 parturient women were examined with deliveries in the period of 28–34 weeks – early PB (III group – 100 women in labor with PROM and IV group – 102 women in labor with the onset of labor with intact fetal membranes) and 60 women in labor with term deliveries.Immunohistochemical detection of CD8, CD3 and CD14 antigens in villi was used to assess the prevalence of the inflammatory process and compare it between groups.Results. In 56.7% of placentas from term deliveries no markers of villousitis were detected, a mild form of villousitis was found in another third of cases. In placentas of woman with the onset of labor between the 28th and 34th weeks with intact fetal membranes there were signs of villousitis in 54.9%, and its mild manifestations in 33.3%. In the case of premature rupture of the membranes, the prevalence of villousitis reached 65%, its severe forms were more often observed.On the other hand, in the groups of very early PB only 14.9 and 15.7% of placentas had no signs of vilouisitis, one in five placentas from these groups had severe focal or diffuse villousitis. In the group of early PB and intact amniotic membranes, one third of the placentas demonstrated an isolated CD3 lymphocyte marker, no antigen was detected in 47.1% of placentas, and only in every tenth placenta antigens of macrophages of fetal origin were determined. A similar distribution was found in placentas from early PB with PROM.In placentas from very early PB the highest frequency of CD14 detection was found – every second placenta contained this marker in isolation and in 22.5% – in combination with maternal lymphocyte markers. In the group of very early PB on the background of PROM placentas with a positive CD14 test dominated – 31.7% isolated and 45.5% in combination with CD3.Conclusions. 1. In placentas from premature births (PB) at 28–34 weeks, villousitis was detected in 54.9% of cases against the background of intact amniotic membranes and in 65.0% – on the background of premature rupture of the membranes, from very early PBs – in 85.1% and 83.3%, respectively. Placentas from deliveries with premature rupture of the fetal membranes more often had signs of severe villousitis – in 21% of cases at 28–34 weeks and in 20.6% at 22–27 weeks.2. In placentas from early PB, macrophage antigen of fetal origin was detected in 22% of cases in the cases of premature rupture of the fetal membranes and in 21.6% of cases of childbirth with intact membranes; these samples were dominated by infiltration by lymphocytes of maternal origin. On the other hand, placentas from very early PB and ruptured fetal membranes in 77.2% of cases contained antigen of fetal macrophages and in 71.6% of cases of onset of labor with intact membranes.Such results indicate the fetal origin of the inflammatory process in very early PB.

Cancer and Immune System: A Comprehensive Analysis of the General Patterns of Carcinogenesis

The proposed review reveals the pathogenesis of the malignant tumor process and the patterns of its initiation and development. It was established that the basis of the malignant tumor process is the physiological process of implantation of the embryo in the thickness of the decidual membrane of the uterus and the regulation of the invasive function of the trophoblast, created by evolution. The determining role of the immune system in regulating these processes was revealed. The possibility of overcoming the malignant tumor process by blocking the key links of the body's immune response to the 37 kDa embryonic antigen has been revealed. The ways and methods of achieving this goal are indicated.

Crosstalk between ESKAPE bacteria and NK cells: mutual regulation and role in developing reproductive tract pathologies

Natural killer (NK) cells represent one of the innate lymphoid cell subsets, which are often studied in the context of antitumor and antiviral immunity, as well as due to their localization in the zone of the mother-fetus contact (in the uterus), therefore underlying their extensive investigation in developing pregnancy. At the same time, their role in antibacterial immune response has been poorly examined. Because NK cells can produce cytokines, one of putative options for their participation in eliminating prokaryotic pathogens may be coupled to regulation of immune system cells such as dendritic cells, macrophages, etc. However, there have been also described variants of contact cytolysis of cells infected with intracellular bacteria enabled due to cytotoxic proteins perforin, granzymes, granulisin found in NK cells. In recent years, it has become known that NK cells take part in development of immune response against extracellular bacteria including the ESKAPE group bacteria, which includes opportunistic prokaryotes that most actively develop antibiotic resistance and cause nosocomial infections. Here, we attempted to review the data on the role NK cells play in antibacterial immunity. Assessing a crosstalk between ESKAPE group bacteria and NK cells also attracts researchers due to the ability of prokaryotes to alter functions of immune cells, but very little is known about the effects they exert on NK cells. At the same time, such data could be applied to seek out for new ways to treat oncological diseases as well as pave the basis for new approaches to regulating NK cell characteristics in reproductive pathologies. As mentioned earlier, the latter occur in the decidual membrane, where they can interact with fetal cells including trophoblast cells. It is believed that cells can mutually regulate each others properties necessary for the course of physiological pregnancy. Probably, imbalance in this system can lead to development of reproductive pathologies. The review summarizes the currently available data on the effects of ESKAPE group bacteria on NK cells, and also considers putative mechanisms for emergence of impaired interaction between NK cells and trophoblasts exposed to ESKAPE group bacteria. Owing to few publications available on this phenomenon, the experimental study assessing an impact of ESKAPE group bacteria on NK cell properties is envisioned as a necessary stage in development of contemporary biology.

Mechanism of BLIMP1/TRIM66/COX2 in human decidua participates in parturition†.

The mechanism underlying the initiation of parturition remains unclear. Cyclooxygenase 2 and prostaglandins in decidual membrane tissue play an important role in the "parturition cascade." With the advancement of gestation, the expression of the transcriptional suppressor B lymphocyte-induced maturation protein 1 in the decidual membrane gradually decreases. Through chromatin immunoprecipitation sequencing, we found that B lymphocyte-induced maturation protein 1 has a binding site in the distal intergenic of PTGS2(COX2). Tripartite motif-containing protein 66 is a chromatin-binding protein that usually performs transcriptional regulatory functions by "reading" histone modification sites in chromatin. In this study, tripartite motif-containing protein 66 exhibits the same trend of expression as B lymphocyte-induced maturation protein 1 in the decidua during gestation. Moreover, the co-immunoprecipitation assay revealed that tripartite motif-containing protein 66 combined with B lymphocyte-induced maturation protein 1. This finding indicated that tripartite motif-containing protein 66 formed a transcription complex with B lymphocyte-induced maturation protein 1, which coregulated the expression of COX2. In animal experiments, we injected si-Blimp1 adenoviruses (si-Blimp1), Blimp1 overexpression plasmid (Blimp1-OE), and Trim66 overexpression plasmid (Trim66-OE) through the tail vein of mice. The results showed that B lymphocyte-induced maturation protein 1 and tripartite motif-containing protein 66 affected the initiation of parturition in mice. Therefore, the present evidence suggests that B lymphocyte-induced maturation protein 1 and tripartite motif-containing protein 66 partially participate in the initiation of labor, which may provide a new perspective for exploring the mechanism of term labor.

Ведення вагітності та розродження жінок з оперованою маткою і локалізацією плаценти на передній стінці матки (огляд літератури)

Purpose – to bring to the attention of obstetrician-gynecologists the relevance of influence of the placental location on the anterior uterine wall in women with an operated uterus after cesarean section (CS) on the course of pregnancy and childbirth with the prevention and minimization of possible complications. The placental location on the anterior wall of the uterus in pregnant women with a uterine scar after CS is the object of research in modern obstetrics. This factor of placental location can affect the course of pregnancy and childbirth, as well as creation increased risk of complications related to the health of the mother and fetus. An operated uterus with placental location on the anterior uterine wall can become a potential etiological factor of perinatal morbidity, which can be accompanied by intrauterine growth restriction, an increase in miscarriage and preterm birth, placenta previa and placenta accreta spectrum frequency, as well as an increased risk of uterine rupture in attempting vaginal birth after cesarean. As commonly stated, optimal conditions for fetal development are created by the placental location at uterus fundus, though labor dystocia is often observed during childbirth in this case. An increase in the percentage of CS and pregnancy in women with a uterine scar is often the cause of the decidual membrane defect and increases the frequency of placenta accretion (placenta accreta/increta/percreta) cases up to 30% in the cohort. One of the possible factors contributing to the attachment of the placenta to the anterior uterine wall is the presence of uterine scar after previous CS. Numerous studies indicate a significant increase in the frequency of placenta accreta cases over the past 20 years due to increase in CS cases and wide implementation of assisted reproductive technologies. Studies according to established criteria are still insufficient in modern obstetrics due to the limited number of pregnant women with localization of the placenta along the anterior wall after CS. More attention in studies is paid to the course of pregnancy and the method of delivery of pregnant women with a scar on the uterus. That states the focus of this article on the importance of clarification the pathogenesis, prevention of complications and delivery of pregnant women with uterine scar after CS and the placental anterior uterine wall localization. These findings confirm the need for further scientific research on this obstetric problem. Understanding the mechanisms behind this etiological connections can contribute to the development of better strategies for monitoring, diagnosis and various options for the delivery with the minimization of possible perinatal complications. No conflict of interests was declared by the authors.

Особливості функціонування імунологічної толерантності під час вагітності (огляд літератури)

Pregnancy is a special state in a woman’s life, which can definitely be considered an «immunological paradox», because the growth of a genetically «alien» fetus takes place in a woman’s body. Despite the direct contact between cells of fetal origin (syncytiotrophoblast) and cells of the maternal immune system, which are in excess in the decidual membrane of the uterus, rejection of the semi-allogeneic fetus does not occur. A state of permanent natural immunological tolerance, during which the body does not respond to certain antigens expressed by trophoblast cells, while maintaining the ability to respond immunologically to other immunogens is the opposite phenomenon of the immune response, it is acquired by the body during its development and is not genetically determined. Purpose - to analyze the phasing of immunological changes in the mother’s body, which are aimed at the development and preservation of pregnancy, to specify their role in the correct flow of placental waves, prevention of the development of placental dysfunction and obstetric complications associated with it. A review of modern medical literature on the processes of immunological changes during trophoblast invasion and placentation in early pregnancy is given. For a more detailed understanding, the influence of each link of the immune response in the process of developing immune tolerance was analyzed. It has been established that for the development of a normal pregnancy there is a genetically programmed immune mechanism that ensures a decrease in the local and systemic immune response to the semi-alien implanted blastocyst, embryo and fetus. This is achieved through the step-by-step course of three phases of immunological shifts: the unfolded immune conflict; suppression of the immune response and intense immune conflict. The physiological course of gestation and the development of the placenta, in which the balance between the processes of neoangiogenesis and apoptosis is maintained, is ensured by adequate expression of HLA-G locus molecules by trophoblast cells, inhibition of Th1-type cytotoxic reactions against placenta cells by the mother's body. Analyzed changes in the cytokine balance, which shifts towards immunosuppressive cytokines, which suppress cellular immune reactions and stimulate the production of blocking antibodies, the quantitative composition of which can be considered decisive when carrying a genetically foreign fetus. Consequently, a relative secondary cellular immunodeficiency is formed, which is mainly due to a deficiency of circulating T-helper/inducers, a decrease in the CD4/CD8 immunoregulatory index and suppression of the functional activity of the T-cell immune system. It has been proven that impaired immunological tolerance, trophoblast invasion and vascular remodelling processes controlled by the maternal immune system at the local and systemic levels lead to early reproductive losses, premature birth, placental dysfunction, and are associated with fetal growth retardation syndrome, pre-eclampsia and other complications. No conflict of interests was declared by the authors.

CLINICAL PATHOGENETIC SUBSTANTIATION OF THE REGENERATIVE TREATMENT OF PARTURIENTS WHO SUFFERED FROM OBSTETRICAL HAEMORRHAGES

The publication is devoted to an urgent problem of modern obstetrics – the study of pathophysiological changes in the organism of parturients after obstetrical haemorrhages, improvement of restorative treatment, as well as reduction of complications in the puerperium and prevention of their occurrence. The aim of the study: to increase the effectiveness of restorative treatment of women in labor who suffered obstetric bleeding by studying the features of the clinical course, mechanisms of pathogenetic disorders, and their correction using ozone therapy. Materials and methods. A comprehensive clinical and laboratory examination of 150 women in labor was carried out, including 120 women (the main group) who suffered bleeding during childbirth and the early postpartum period. The control group consisted of 30 women with the physiological course of labor, childbirth and the early postpartum period. The state of lipid peroxidation (LPO) in parturient women was evaluated by the content of primary lipid products in the blood plasma – diene conjugates (DK) according to the method of B.V. Gavrilov (1983) and secondary molecular products – malondialdehyde (MDA) using the reaction with 2 thiobarbituric acid. The activity of the enzymatic link of the antioxidant system (AOS) was determined by the content of catalase in peripheral blood erythrocytes using the substrate hydrogen peroxide and glutathione peroxidase (GPO) using the P phenylenediamine substrate. The Spielberg–Hanin scale of state and trait anxiety was used to study the state of the psycho-emotional sphere in parturient women. Morphological examination of preparations of placentas and surgically removed uteri was carried out with staining of sections with hematoxylin and eosin, picrofuchsin according to Van Gieson. Results. Basic etiopathogenetic factors of the development of obstetric haemorrhages were examined, changes in the psychoemotional status of the patients were detected, haematological and metabolic indices, parameters of oxidation-antioxidation homeostasis and endogenic intoxication were studied, as well as morphofunctional disorders in placentas and uteruses. The efficacy of the restorative treatment of the parturients, who had moderate and massive haemorrhages during delivery, with the use of medical ozone in combined treatment versus traditional methods of treatment was studied. Conclusion. From the first day of the puerperium, free-radical lipid peroxidation increases, the activity of the enzymatic and non-enzymatic links of the antioxidant system increases, endogenous intoxication increases, and lactate and pyruvate levels increase. In the placentas of women in labor who suffered bleeding during labor, there is a violation of the synthesis of type IV collagen in the basal membranes of vessels and the phenomenon of endothelial dysfunction in the form of increased expression of endothelin by the endotheliocytes of the vessels of the decidual membrane (53.8 ± 2.9 µa) and the villous chorion (46.0 ± 2.6 μa). In the uterus, an increase in the expression of endothelin by endotheliocytes of the spiral arteries of the uterus (57.8 ± 8.56 µa) was detected, in combination with a violation of the synthesis of stromal collagen of type I and III and type IV in the basal membranes of vessels.

Features of immunohistochemical markers of stem CELLS CD-117, CD-44 in female placentas on the background of chronic stress

Background. Placenta is a subject of interest to a wide range of scientists because it is rich in stem cells and their precursors. A stem cell is a cell that has the ability to self-repair and can differentiate into offspring (daughter cells) of one or more germ layers. In recent years, scientists have obtained new data of stem cells regenerative potential. However, only isolated publications about placental stem cells are available. Therefore, our studies about placental stem cells are important for discovery of structural and molecular mechanisms, their changes under the influence of chronic stress.Objective: to study the features of immunohistochemical markers of pluripotent stem cells and their morphological features.Materials and methods. We examined 80 women placentas with chronic stress in comparison with control using general histological and immunohistochemical methods in the following groups: group 1 – women placentas with physiological course of pregnancy in term 38–40 weeks, group 2 – women placentas with miscarriage, group 3 – women placentas with chronic stress due to internal irradiation (4.5 Bq/kg and more), group 4 – women placentas which had COVID-19 during pregnancy.Results. There was a significant increase of stem cell markers expression in the three study groups with a significant predominance in groups 3 and 4. It was also determined the different direction of their active factors.Conclusions. The general changes of all structures of the placental barrier are detected as a result of chronic stress due to various factors: micro detachment of the decidual membrane (significant increase in cases in the studied groups); malperfusion in the structures of the maternal placental barrier; in the placenta stem cells of the three study groups in comparison with the control were found stress markers. Thus, chronic stress due to various factors causes the same type of changes in placental structures, but they have different degrees of expression – with internal irradiation doses ≥ 4.8 Bq/kg, these changes are most expressive.

Changes in the Expression of Pluripotency Factor Oct-4 and Intensity of Apoptosis in the Uterus during Spontaneous and Immune-Dependent Abortions in Mice.

We studied the expression of pluripotency factor Oct-4 and the intensity of apoptosis in the uterus during spontaneous and immune abortions in mice. Increased expression of factor Bax and reduced protein Bcl-2 synthesis in cells of the decidual membrane and decreased Oct-4 expression in the myometrium and perimetrium were detected. Thus, both spontaneous and immune-dependent abortions impair the apoptosis processes in the decidua and the formation of a pool of Oct-4+ cells in the uterus. In immune-dependent abortions, the intensity of apoptosis of decidual cells was lower than in spontaneous abortion. Low expression of the transcription factor Oct-4 in the myometrium and perimetrium characterizes pregnancy failure irrespective of its mechanisms.

Placental markers of miscarriage

Successful implantation involves a high degree of development of spiral arteries, combined with high proliferative activity, which ensures the formation of a healthy placenta, full uterine-placental circulation, and the birth of a healthy child. The placenta is the unique organ of the biological monitoring, the mirror of pregnancy. Identification of placental markers of miscarriage is a promising direction for preventing reproductive losses. The aim of the work is to identify the markers of miscarriage and premature labor in the structures of the chorion and placenta. Materials and methods. The main group included tissue samples of the 22 chorions and 64 placentas after termination of current pregnancy from women with a history of reproductive losses. The control group included tissue samples of the 20 chorions after artificial abortion and 20 placentas after physiological pregnancy and birth. The placenta was examined according to the protocol (form No. 013-1/0). The expressions of VEGF, CD31/PECAM1, CD105/Endoglin/TGFβ 1/3 Receptor, Bcl-2α Ab-1, TNF-α, CD45/T200/LCA, CD56/NCAM1 were studied in the structures of chorion and placenta by immunohistochemistry. Results. Based on histological and immuno-histochemical study of chorion and placenta samples in women with reproductive history and termination of the current pregnancy, it was established that embryo-endometrial dysfunction is the cause of miscarriage in the first trimester, and inflammation is the precondition of preterm birth; markers of miscarriage and premature labor in the structures of the chorion and placenta have been identified. Conclusions. The markers of miscarriage are pathomorphological changes in endometrium and chorion combined with high expression of TNF-α and NK-CD56, low expression of CD31/PECAM1, negative expression of VEGF to indicate a violation of cytotrophoblast invasions. The markers of inflammation and premature labor are structural and functional changes of placenta in combination with moderate expression of TNF-α in syncytium, high expression of NK-CD56 in villous stroma, high expression of CD45/T200/LCA in the decidual membrane.

Pathogenetically justified tactics of management of pregnancy with retrochorial hematoma

Introduction. Retrochorial hematoma (RH) often detected during routine ultrasound examination represents one of the multiple causes resulting in early pregnancy loss. RH results from the detachment of the chorionic plate from the vertebrae of the uterine decidual membrane and may lead to complicated course of pregnancy.Aim: to develop a differential approach to diagnose and manage pregnancy with RH.Materials and Methods. A prospective open-ended interventional non-randomized study was conducted by enrolling 170 women. The main group consisted of 85 pregnant women with RH, which were divided into 2 groups: group I (n = 45) – patients with RH and burdened obstetric history; and group II (n = 40) – pregnant women with RH without a history of obstetric complications. The control group included 85 women with uncomplicated pregnancy. The incidence of hereditary thrombophilia was assessed by measuring rate of high thrombogenic risk mutations in the genes of factor (F) V Leiden and prothrombin (FII) G20210A; blood levels of lupus anticoagulant (LA) and anti-cardiolipin antibodies (aCL), β2-glycoprotein 1 (β2-GP1), annexin V and prothrombin; ADAMTS-13; rate of low thrombogenic risk polymorphisms, prevalence and spectrum of bacterial-viral infections.Results. It was revealed that women with RH had occasional genetic and acquired hemostasis defects as well as impaired florocenosis of the urogenital tract. Defects in the fibrinolysis system prevailed among the hereditary hemostasis defects: 75.5 % in group I, 32.2 % in group II, and 4.7 % in the control group. No decrease in the activity of natural anticoagulants – antithrombin and protein C was found. Among the acquired thrombophilic conditions, a large proportion of circulating antiphospholipid antibodies (APA) was found: 46.6 % in group I, 27.5 % in group II, and 2.3 % in the control group. Cervicitis of nonspecific etiology prevailed among dysbiosis signs: 53.3 % in group I, 47.5 % in group II and 11.7 % in the control group.Conclusion. RG formation is a multifactorial process, which pathogenesis involves both genetic and acquired factors such as APA, especially in combination with genetic thrombophilia (FV Leiden and FII G20210A), as well as inflammatory or pro-inflammatory status. We consider that all patients with RG as well as those with former RG are indicated to undergo the above-mentioned studies. It is advisable to include tranexamic acid, progesterone, low molecular weight heparins and antibiotics in the therapy regimen if indicated.

Electronic microscopic specifications of decidual spilla in a woman with placenta previa

The objective: a study of the electronic microscopic features of the decidual membrane in pregnant women with placenta previa. Materials and methods. 122 pregnant women with atypical location of the placenta were examined and delivered within 36 weeks+6 days and 38-39 weeks of gestation in Kyiv Perinatal Center during 2014–2020. Electronic microscopy of the decidual membrane was performed in 10 pregnant women with placenta previa. Decidual membrane biopsy was performed directly from the site of placenta previa and from the uterine body outside the placenta previa. Results. By placenta previa the endometrial glands penetrate deep into the myometrium in the border zone of the endometrium with the myometrium, some of them lose the basement membrane in the epithelium, and the enlarged tubules of the granular endoplasmic reticulum are located in its cytoplasm. Most of them are without ribosomes, which formed autophagosomes in the cytoplasm or outside it. A large number of dictyosomes were found. In most of the epithelial cells, the plasma membrane is not preserved and the cytoplasm is in direct contact with the myometrium or connective tissue or is lysed.Examination of the decidual membrane in the body of the uterus outside the placenta previa demonstrated that the decidual cells are surrounded by a basement membrane, have a polygonal shape, contain many glycogen inclusions in the form of small dense granules – beta-particles and granules which form the clusters in the form of rosettes – alpha-particles. Their content is washed out of fat inclusions, and the cytoplasm of decidual cells, in the late period of observation, loses the content of trophic inclusions and, accordingly, energy supply. The lumens of blood vessels are filled with electronic dense content or are completely obstructed by accumulations of blood plasma proteins, fibrin, cellular detritus of blood cells, which contributes to the formation of blood clots. The smooth muscle cells of these vessels are compacted and located in the clefts of the basement membranes of epitheliocytes and their own basement membranes. Conclusions. In the decidual membrane directly in the area of ​​placenta previa in the lower segment of the uterus, the foci of decidualization significantly expand and push the endometrial glands into the myometrium. The basement membrane of the endometrial epithelium is lysed, its structural organization is disrupted and its contents are homogenized, which leads to an increase in the permeability of the decidual membrane. Blood-forming elements, in particular leukocytes, cellular detritus and the significant growth of collagen and elastic fibers impede interstitial transport of the intercellular substance that leads to the systemic disorganization of connective tissue, damage of vessels of a hemomicrocirculatory channel and the increase in immunopathological processes. In turn, the loss of the inclusions by the decidual cells leads to a disorder of trophic decidual membrane in the uterine body by placenta previa in the lower segment of the uterus.

Preeclampsia: inflammatory signature of decidual cells in early manifestation of disease

IntroductionPreeclampsia is a pregnancy-specific complication characterized by hypertension in combination with proteinuria and/or various manifestations of multiple organ failure. It is believed that etiology of preeclampsia lies in dysfunction of the placenta and disorder of the maternal-fetal interactions. In preeclampsia decidual membrane, the maternal part of the placenta which normally supports immunological tolerance of the maternal organism to the semi-allogeneic fetus, becomes a site of inflammation. MethodsThe aim of our study was to characterize the phenotype of decidual macrophages and plasma profiles in patients with late- and early-onset preeclampsia as compared with controls (n = 43). Decidual cells were obtained by enzymatic digestion method and characterized by flow cytometry analysis, real-time PCR, bioinformatics analysis, immunohistochemistry, and Western blot. Plasma samples were analyzed by multiplex assay. ResultsThe number of inflammation-associated CD86+ and CX3CR1+ cells was significantly higher in the early-onset preeclampsia while the portion of CD163+ cells was significantly higher among studied groups. We observed significant increase of endothelin-1 gene expression and a significant decrease in eNOS and GNB3 expression and TGFβ relative protein level in decidual cells of the early-onset preeclampsia samples. We also revealed elevation of pro- and anti-inflammatory cytokines in plasma of preeclampsia groups. DiscussionOur findings reflect profound early-onset preeclampsia-associated alterations in the decidua and emphasize the importance of the decidua as a link in the development of preeclampsia.

Morphological and immunohistochemical features of placenta in postpartum women with hyperprolactinemia history

Hyperprolactinemia (HP) is a persistent increase in serum prolactin levels, the most typical manifestation of which is a dysfunction of the reproductive system. Pregnant women with HP have a high incidence of perinatal complications; thus, the threat of self-abortion in these women is more than 48.4 %, and in 16.1 % of pregnant women it ends in premature birth. These patients often develop placental abnormalities that lead to fetal distress during pregnancy and childbirth.The aim: to investigate the morphological and immunohistochemical changes in the placental barrier, taking into account the expression of prolactin in postpartum women with a history of hyperprolactininemia.Materials and methods. In 30 puerperas with a history of endocrine infertility associated with hyperprolactinemia (group 1) and in 27 healthy puerperas without hyperprolactinemia and infertility (control group 2), the morphological features of the placentas were studied in the gestational period of 39–40 weeks using organometric, macroscopic, histological and immunohistochemical (IHC) methods.IHC studies were carried out on serial paraffin sections in accordance with standard protocols using monoclonal antibodies to prolactin (Rabbit a-Нu Prolactin Monoclonal Antibody (Clone EP 193) master diagnostica (Spain) and detection system Thermo scientific (USA).Results. The placenta weight of women in labor with hyperprolactinemia did not differ significantly from the weight of the placenta of women in labor without hyperprolactinemia. In 22 (73.3 %) postpartum women with hyperprolactinemia in the placenta, paracentral attachment of the umbilical cord took place, in 4 (13.3 %) patients malformation of the umbilical cord vessels was detected, in 7 (23.3 %) postpartum women significant stenosis and closure of the arterial lumen vessels of the umbilical cord were found. Histological examination of women in labor with hyperprolactinemia identified focal thickening of the decidua with the presence of significant fibrinoid masses (n = 18, 60 %), microbleeds and thinning of the decidua (n = 8, 26.6 % of women in labor). A number of observations revealed the presence of maternal internal infarctions with perivillous fibrin deposition, in 12 (40 %) postpartum women, the presence of fibrinoid-embedded villi with the replacement of the villus epithelium with fibrinoid masses was noted, in 15 (50 %) women fibrosis and collagenization of the stem and middle chorionic villi, fibrosis of small villi and avascular small villi was observed in 12 (40 %) postpartum women. In some observations, a decrease in the number of syncytial nodes and syncytiocapillary membranes was noted in the terminal villi. IHC study of the placenta of postpartum women with hyperprolactinemia in the gestational period of 39–40 weeks revealed multiple foci of decidual cells with overexpression of prolactin in the cytoplasm.Conclusions. Morphological changes in the placenta of postpartum women with hyperprolactinemia in anamnesis differ from changes in the placenta of women without hyperprolactinemia by the presence of focal vascular changes in the decidual membrane with its partial detachment and internal infarctions in the maternal part of the placenta, as well as by the presence of signs of partial perfusion disorders of the fetal foci placenta.In the placenta of women with hyperprolactinemia, immunohistochemical study revealed a long-term focal significant cytoplasmic expression of prolactin in the cells of the decidual membrane, which indicates disorders of prolactin synthesis in the body and discoordination in the work of the endocrine system of women.

Features of the cytokine profile in the structures of chorion and placenta in premature termination of pregnancy

The placenta is a mirror of pregnancy. The formation of a healthy placenta predetermines embryo-endometrial relationships, which are regulated by cytokines. The study of the role of cytokines in the regulation of the gestation process in miscarriage is relevant.The aim of the work is to establish markers of miscarriage based on the study of features of the cytokine profile in the structures of the chorion and placenta in premature termination of pregnancy.Materials and methods. 22 chorions and 26 placentas from women with a history of reproductive loss and termination of current pregnancy were examined (the main group). The control was the tissue of the chorion, taken after artificial abortion in 20 women, and 20 placentas from uncomplicated pregnancy and physiological births in women with the first pregnancy. The placenta was examined according to the protocol (form No. 013-1/0). Expression of TNF-a, CD31/PECAM-1, CD45/T200/LCA in chorion and placenta structures were determined by immunohistochemistry.Results. The termination of pregnancy in the first trimester is accompanied by a violation of the ratio of cytokines - an increase in the expression of TNF-α and a decrease in the expression of CD31/PECAM-1 in the structures of the endometrium and villous chorion. The results indicate a shift in the immunological balance towards an inflammatory response and a violation of the cytotrophoblastic invasion. Inflammation plays a leading role in the development of preterm birth. Structural and functional changes in the placenta against the background of inflammation make up the morphological substrate of chronic placental dysfunction, which, in a case of decompensation, triggers the process of preterm birth.Conclusions. The cytokine marker of terminating pregnancy in the first trimester is the high expression of TNF-α in the structures of chorion and endometrium in combination with low expression of CD31/PECAM-1 in the endothelium of the spiral arteries, in the intravascular and interstitial cytotrophoblast. The marker of inflammation is a moderate expression of TNF- α in the invasive cytotrophoblast, decidual cells and terminal villi of placenta in combination with high expression of CD45/T200/LCA in the decidual membrane.

Особенности морфофункционального состояния маточно-плацентарной единицы и эмбриона мыши на ранних сроках экспериментального невынашивания беременности

Introduction. The majority of cases of habitual miscarriage are closely related to impaired maternal immune tolerance. Experimental mice models of abortion, where the critical time points are established to monitor pregnancy progression, are widely used to study the pathogenesis of early reproductive loss. However, the relationship between the embryonic development and extraembryonic structures with the immune microen-vironment is not well understood. The aim of the study is to compare the morphofunctional characteristics of the uteroplacental unit and embryo in early pregnancy in mice with experimental spontaneous, induced, and potentiated abortions. Materials and methods. Allogeneic physiological pregnancy was modeled using ♀CBA × ♂BALB/c mice mating. Spontaneous abortions were reproduced by mating ♀CBA × ♂DBA/2 mice. Induced abortions and potentiated abortions were triggered by intraperitoneal administration of the immunomodulator ß-heptylglycoside muramyl dipeptide (MDP) to pregnant females on gestation day (gd) 5 and gd 7 mated in following combinations ♀CBA × ♂BALB/c and ♀CBA × ♂DBA/2, respectively. Mice were withdrawn from the experiment on gd 8, then uterine horns and uteroplacental units were isolated. The material was fixed in 10% neutral formalin, and standard processing was performed for histological examination. In equatorial sections, the cross-sectional area of uteroplacental unit was measured, and maternal, embryonic, as well as extraembryonic structures were analyzed. An immunohistochemical assay with rabbit polyclonal anti-CD68 antibodies was conducted to detect macrophages, then the density of CD68+ cells per 1 mm2 of the decidual area was determined. Results. On day 8 of pregnancy, in the groups of induced and potentiated abortions cross-sectional area of the uteroplacental units was decreased compared with the groups of physiological pregnancy and sponta-neous abortions. Induced and potentiated abortions demonstrated vasodilation in the mesometric decidua zone and stagnation of blood in the blood vessels, compaction of trophoblast, and hemorrhage in decidua basalis whether spontaneous abortions showed occluded maternal vessels surrounded by edematous and vacuolated trophoblast cells.At the early stages of modeling of spontaneous and immuno-dependent abortions, disturbances in the devel-opment of the embryo and extraembryonic structures were revealed, ranging from initial signs of resorption to the destruction of the embryo and membranes.In viable embryos, density indices of CD68+ macrophages in the decidual membrane of the uteroplacental units did not differ significantly in all miscarriage cases, CD68+ cells were not detected in cases of embryo-nal resorption. Conclusion. The MDP treatment in a period after completion of implantation and before forming a mature placenta (gd 5–7) results in the inducing or the potentiating abortions in CBA females mated with by Balb/c or DBA/2 males, respectively. In both cases, we revealed disturbed chorion morphogenesis and embryonic development to the extent of its complete resorption and the absence of CD68+ macrophages in resorbed embryos’ microenvironment on day 8 of pregnancy. Keywords: miscarriage, models, muramyl dipeptide β-heptylglycoside, uteroplacental unit, macrophages, immunotolerance

Morphology of Endometrial Scrapings in Early Spontaneous Abortions

Objective: Study of morphological changes in the endometrium and fetal membranes during spontaneous abortions in 9-12 weeks of pregnancy to clarify the etiopathogenetic mechanisms. Materials and methods: Study material was endometrial scrapings with components of fetoplacental tissue obtained after spontaneous abortions (176 cases) in 9-12 weeks of pregnancy, received at the Republican Pathological Bureau from several City Maternity Hospitals of Bishkek (Kyrgyz Republic). The histological sections were stained with hematoxylin and eosin (H&E), and a mixture of acid fuchsin and picric acid. The Periodic acid–Schiff (PAS) reaction was performed. Results: Of the 176 cases in 80 cases, by the medical reports, pregnant women had concomitant gynecological infectious pathology in the form of chronic endometritis, chronic salpingoophoritis, chlamydia, colpitis, and adnexitis. Histological examination revealed inflammatory changes in the form of deciduitis (24.5% of cases), endometritis (20.5% of cases), villitis (17.3% of cases) in 70% of cases. Pathological changes in the decidual membrane are determined as foci of leukocyte infiltration in 65% of cases, in 30% - foci of necrosis and in 20% - foci of hemorrhage. In 60% of cases, as their combination. Conclusion: Histological examination of endometrial scrapings and fetal membranes after spontaneous abortions in 9-12 week pregnant women, with a history of infectious inflammatory pathology, revealed the tissue inflammatory changes of varying severity, with the following additional microscopic characteristics: the compact arrangement of endometrial glands, weak vascularization of villus chorion; sclerotic, dystrophic, and necrotic changes with hemorrhages in the endometrium and decidual membrane.

Peculiarities of the inflammatory reactions development in placenta at delivery in different gestational terms

Objective of the study: to study peculiarities of the inflammatory reactions development in placenta according to results of a general histological and immunohistochemical study of the prevalence and intensity of reactions caused by CD45 and tumor necrosis factor α (TNF-α) during childbirth at different gestational periods.Materials and methods. Morphological and immunohistochemical studies of various placental structures and CD45 and TNF-α expression level in 142 women with preterm delivery at different gestational periods were performed: group I – at 23–29 weeks, group II – at 30–34 weeks; group III – at 35–36 weeks + 6 days, group IV (control) – 40 women at 38–40 weeks.Results. Inflammatory infiltration and the most expressive CD45 expression prevailed in the decidual membrane, TNF-α expression was predominantly negative in group I. In group II, inflammatory changes were evidenced by collagenization and stromal fibrosis, a decrease in fetal vessels, fibroblast proliferation, an increase in intervillous fibrinoid, and CD45 spread was expressed in decreasing order of intensity in decidual membrane, in stroma of intermediate villi and in stem villi. In group III, foci of inflammatory infiltration spread from the decidual membrane to the intervillous space and villi stroma, vessels plethora of all types of villi, dystrophic changes, and fibrinoid volume increased. CD45 expression was more common and expressive than in the groups I and II, and TNF-α expression was weakly positive only in the decidual membrane. The control group determined the widespread expressive CD45 expression in all placental structures and positive moderate TNF-α expression.Conclusions. Preterm delivery and delivery on term occur when there is an activation of inflammatory reactions in placenta. Inflammation in the placental structures is a necessary condition for development of the mother-fetal interphase, however, the features of local immune response prove the need to determine genetic mechanisms of the preterm labor.

Importance of cytokines in the pathogenesis of preeclampsia in pregnant women with iron deficiency anemia

Hypothesis/aims of study. The frequency of hypertension in iron deficiency anemia (IDA) reaches 3245%. The pathogenesis of pregnancy complicated with anemia and preeclampsia, including immunological aspects, has been little studied. The aim of this study was to clarify the role of general and local cytokine status violations in pregnant women with anemia in the genesis of preeclampsia and to justify the need for inclusion of immunosuppressive agents for the prevention and treatment of preeclampsia.
 Study design, materials and methods. The cytokine status (IL-1, IL-6, IL-8, TNF) and the level of lactoferrin in peripheral blood serum and in extracts of the placental decidual tissue were examined by ELISA in 96 pregnant women with IDA and preeclampsia in the third trimester of gestation. Pregnant women were divided into four groups: 24 with mild anemia, 18 with moderate anemia, 26 with preeclampsia and mild anemia, and 28 with preeclampsia and moderate anemia.
 Results. It has been shown that preeclampsia, along with IDA, is accompanied by a significant increase in the level of pro-inflammatory cytokines and the acute phase protein lactoferrin at the systemic and, to a greater extent, local level, that is in the decidual membrane of the placenta, in the development of preeclampsia against the background of moderate anemia. The data obtained confirm the involvement of the immune system in the pathogenesis of preeclampsia, one of the triggers of which is the immune imbalance in IDA. A pathogenetic rationale for the use of immunosuppressive therapy for combined pathology is given.
 Conclusion. The use of placental hormone progesterone as an immunosuppressive drug in terms of substantiating new immunotherapy strategies for the prevention and treatment of preeclampsia is a topical trend in obstetric practice.