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Abstract Preeclampsia (PE) is one of the most dangerous complications of pregnancy, characterized by hypertension, proteinuria, and symptoms of multiple organ failure, which are detected de novo after 20 weeks of pregnancy. The renin–angiotensin–aldosterone system (RAAS) is one of the first to recognize pregnancy and is an important regulator of blood pressure. The placenta has its own RAAS, the role of which in the development of PE is not fully understood. In this work, for the first time, we characterized the expression of RAAS components and miRNAs controlling it in the placenta at various times of PE manifestation. The data obtained will allow the development of a new strategy in the future for the search for therapeutic agents for patients suffering from PE and cardiovascular diseases.

Although hypoxia tolerance is mainly determined genetically, it is important to study individual variability of animal organisms in order to identify the factors that underlie their tolerance to hypoxic exposure. We investigated blood cell counts and coagulograms in Wistar rats as predictors allowing the animal population to be split into hypoxia-tolerant and hypoxia-intolerant individuals. The validity of the specific predictors’ choice was proved by a coincidence between the population split in accordance with the detected individual parameters and the results of testing animals in a decompression chamber at a rarefaction corresponding to the “rise to an altitude” of 11500 m above sea level. Circulating blood cells were quantitatively assessed by eighteen indicators before and after hypoxic exposure. The differences between animals low-tolerant (LT), high-tolerant (HT), and medium-tolerant (MT) to hypoxia were determined by five indicators: white blood cell count (WBC), granulocyte count (Gran#), red blood cell count (RBC), reticulocyte count/percent (RTC), and mean corpuscular hemoglobin (MCH). The RBC, RTC, and MCH values in HT rats were significantly higher than in LT animals (by 1.4, 1.9, and 1.1 times, respectively). The WBC and Gran# values in HT rats were lower than in LT individuals. The hypoxia tolerance indices (HTI) were calculated using the original formula. It was established that in LT rats, the HTI ≤ 0.203, in HT rats ≥ 0.335, and in MT rats < 0.335 but > 0.203. After testing in a decompression chamber, the activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) decreased, but the fibrinogen level increased. LT rats were characterized by the lowest APTT, TT, and PT values and the highest values of the fibrinogen level. Our results indicate that one of the most important mechanisms underlying a high hypoxia tolerance in rats consists in sustaining reciprocal relationships between the complex of RBC indicators, which tend to increase under hypoxia, and Gran# indicators, which tend to decrease after hypoxic exposure.

For the first time in modeling posttraumatic stress disorder (PTSD), we have described the morphofunctional state of adrenal glands in Wistar rats resistant and sensitive to predator stress (rodent fear of the predator). Despite the evident signs of adrenal dysfunction in both phenotypes, we have discovered the thickening of undifferentiated cell zone and high indices of functional activity of stem cells in resistant animals, suggesting ample adaptation. The most important data demonstrate the direct relationship between the reduction of corticosterone and testosterone levels and adrenal dysfunction in PTSD models. The study results allow considering the adrenal stem cells as potential therapeutic targets.

We studied the dynamics of morphological changes in the operated segment of the uterine horn of Sprague-Dawley rats during the first 2 weeks of the wound-healing process after a full-thickness surgical incision with regard to the estrous cycle phase. Morphometric parameters of injured uterine right horn were compared with those in the intact left horn of the same animal as a control of changes determined by the hormonal background. It was found that the uterine epithelium in the focus of injury was restored as soon as on day 2 after surgery under the influence of estrous cycle hormones. By day 4, the wound space was completely filled with the endometrial tissue on the side of the uterine lumen and coved by the attached adipose tissue of the mesentery on the side of the abdominal cavity. The thickness of the uterine wall and the uterine lumen differed most strongly between the operated and intact uterine horns during the first 3 days and on day 6 after surgery. The size of the healing area increased during the first three days and reached the peak value by day 3, but then decreased to minimum by day 6.

We compared behavioral and psychoemotional manifestations of young and old male Wistar rats in elevated plus-maze, the levels of corticosterone and testosterone, as well as the resistance to acute hypoxic hypoxia before and after stress exposure (10-min swimming sessions over 10 days). The behavioral characteristics, responses of the main stress hormone corticosterone, and resistance to acute hypoxic hypoxia were identical in both age groups before and after stress. A distinguishing feature was pronounced flattening of the psychoemotional manifestations in old animals. The main adaptive differences between young and old rats were revealed in the response of circulating testosterone to stress.

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

Spontaneous proliferative activity of splenocytes in female CBA mice and the response of these cells to antigens of allogeneic male BALB/c and DBA/2 mice in a mixed splenocyte culture were evaluated by 3H-thymidine incorporation in different pregnancy models. ♀CBA×♂BALB/c mating was used for modeling physiological pregnancy. Spontaneous abortions were reproduced by abortion-prone ♀CBA×♂DBA/2 mating. In order to simulate immunostimulant-induced and immunostimulant-potentiated abortions, 0.83 mg/kg muramyl dipeptide β-heptylglycoside was intraperitoneally injected to CBA females mated with BALB/c or DBA/2 males, respectively, on gestation days 5 and 7. The increase in the rate of embryo resorption in the models of spontaneous, induced, and potentiated abortions occurred against the background of an increase in the level of spontaneous proliferation of splenocytes and a decrease in their reactivity to paternal antigens on gestation day 9.

For elucidation of the mechanisms of IgG binding with human plasminogen in prostate cancer patients, we propose an original ELISA on polystyrene plates with immobilized heavy and light plasminogen chains. The level of IgG bound to plasminogen heavy chain in the serum of prostate cancer patients significantly exceeded that in healthy volunteers. IgG treated with plasmin more actively (by more than 2 times) bound plasminogen heavy chain than intact IgG. These findings indicate the involvement of lysine-binding sites of plasminogen heavy chain in the interaction with the C-terminal lysine of IgG and their fragments. ROC analysis of ELISA data showed significant differences between serum samples from patients with prostate cancer and benign prostatic hyperplasia. It is hypothesized that IgG in the tumor region undergo proteolysis and their products appear in the circulation.

We studied the dynamics of morphological changes in the operated segment of the uterine horn of Sprague-Dawley rats during the first 2 weeks of the wound-healing process after a full-thickness surgical incision with regard to the estrous cycle phase. Morphometric parameters of injured uterine right horn were compared with those in the intact left horn of the same animal as a control of changes determined by the hormonal background. It was found that the uterine epithelium in the focus of injury was restored as soon as on day 2 after surgery under the influence of estrous cycle hormones. By day 4, the wound space was completely filled with the endometrial tissue on the side of the uterine lumen and coved by the attached adipose tissue of the mesentery on the side of the abdominal cavity. The thickness of the uterine wall and the uterine lumen differed most strongly between the operated and intact uterine horns during the first 3 days and on day 6 after surgery. The size of the healing area increased during the first three days and reached the peak value by day 3, but then decreased to minimum by day 6.

We compared behavioral and psychoemotional manifestations of young and old male Wistar rats in elevated plus-maze, the levels of corticosterone and testosterone, as well as the resistance to acute hypoxic hypoxia before and after stress exposure (10-min swimming sessions over 10 days). The behavioral characteristics, responses of the main stress hormone corticosterone, and resistance to acute hypoxic hypoxia were identical in both age groups before and after stress. A distinguishing feature was pronounced flattening of the psychoemotional manifestations in old animals. The main adaptive differences between young and old rats were revealed in the response of circulating testosterone to stress.

The crucial role of chronic endometritis in the genesis of endometrial dysfunction has been currently established. The inflammatory process serves as a co-factor and leads to a decrease in the receptivity of the sex hormones of the endometrium due to impaired blood circulation of the tissue and fibrosis in the stroma of the endometrium. This article is devoted to the study of the morpho-functional state of the endometrium in women of the reproductive age with abnormal uterine bleeding, in whom endometritis was diagnosed pathomorphologically, which is important for clarifying indications for the pregravid preparation in the future. A comprehensive examination of patients with abnormal uterine bleeding includes: bacterial culture (PCR) of the cervical canal and uterine cavity, hormonal profile, ultrasound examination of the pelvic organs and a complex histological examination of the uterine biopsy at the 7–10th and 19–21st days of the menstrual cycle, followed by immunohistochemical examination with the use of antibodies to the receptors of estrogens and progesterone, glycodelin, CD138, CD4, CD8, CD20.

Muramyl dipeptide β-heptylglycoside (C7MDP) was administered to non-pregnant CBA female mice and pregnant mice after non-abortion-prone mating (CBA×BALB/c) and mating associated with a high rate of spontaneous abortion (CBA×DBA/2). In non-pregnant females, C7MDP increased the production of IL-2, IL-4, IL-5, IL-6, IL-17, IFNγ, TNFα, and GM-CSF at constant production of IL-1α and IL-10. C7MDP increased the production of IL-10 and IL-17 and suppressed the production of IFNγ on day 8 of gestation in non-abortion-prone mouse couples and stimulated the synthesis of IL-4 and IFNγ, reduced IL-5 production, and slightly increased IL-1α secretion after abortion-prone mating. On day 14 of gestation, C7MDP elevated the yield of IL-2, IL-4, IFNγ, TNFα, and GM-CSF in CBA×BALB/c and CBA×DBA/2 couples and IL-17 in the fi rst variant of mating.

to determine the clinical and morphological aspects of endometrial dysfunction caused by chronic endometritis (CE).The study included 239 reproductive-aged patients: 93 were examined for abnormal uterine bleeding; 37 patients of them had a history of miscarriage and secondary infertility, 17 patients had primary infertility (Group 1). The remaining 105 patients with infertility were examined for future in vitro fertilization (Group 2). A comparison group consisted of 41 patients with normal menstrual cycles and reproductive function across the cycle, who had separate diagnostic curettage before forthcoming surgery for uterine myoma. All the women in Groups 1 and 2 underwent standard clinical and morphological investigations, histopathological examination of the material obtained during hysteroscopy with separate diagnostic curettage (Group 1), and aspiration biopsy (Group 2) with the sections being stained with hematoxylin and eosin and by Mallory's method. Immunohistochemical diagnosis was used to assess endometrial receptivity to steroid hormones and glycodelin. Antibodies against CD4, СD8, and CD20 were employed to study local immunity.In Group 1, 52 (55.9%) of the 93 patients admitted to hospital for abnormal uterine bleeding were found to have CE on the basis of a morphopathological examination of the material after separate diagnostic study. In Group 2, CE was established in 59 (56.9%) of the 105 patients after postmortem examination. The patients with CE had a history of reproductive significant infections, such as Chlamydia, Trichomonas, Ureaplasma Mycoplasma, cytomegalovirus, papillomavirus infections, genital herpes, genital candidiasis, and bacterial vaginosis. The CE groups showed functional disorders of the endometrial glandular and surface epithelium. In the middle stage of proliferation, the expression of glycodelin in the glandular epithelial cells was detected to be moderate to strong in 83.3%. During the periovulatory period, no secretion of glycodelin is of fundamental importance for the regulation of reproductive function because this protein has contraceptive activity, by blocking the binding of sperm to the zona pellucida. Accordingly, endometrial glycodelin production during the proliferative phase, which has been identified by the authors in patients with CE, may be one of the pathogenic mechanisms for the development of infertility. In addition, the patients in Groups 1 and 2 compared with those in the comparison group were noted to have a decrease in CD4 cell counts with a simultaneous increase in CD8 expression and a reduction in CD20 levels, especially in Group 2.The patients with SE were identified to have endometrial dysfunction characterized by lower reception to steroid hormones, impairment in glycodelin secretion, retardation in the development of pinopods and in the phase of the menstrual cycle, and local immunity disorders. The above endometrial changes should be taken into account in the pregravid preparation of patients with CE.Цель исследования - определить клинико-морфологические аспекты эндометриальной дисфункции, обусловленной хроническим эндометритом. Материал и методы. В исследование включено 239 пациенток репродуктивного возраста: 93 поступили на обследование по поводу аномальных маточных кровотечений, из них у 37 пациенток в анамнезе имели место невынашивание беременности и вторичное бесплодие, у 17 пациенток - первичное бесплодие (1-я группа). Остальные 105 пациенток с бесплодием были обследованы по поводу предстоящего экстракорпорального оплодотворения (2-я группа). Группу сравнения составили пациентки (41) с нормальным менструальным циклом и репродуктивной функцией цикла, которые перенесли раздельное диагностическое выскабливание перед предстоящей операцией по поводу миомы матки. Всем женщинам 1-й и 2-й групп проведены стандартное клинико-морфологическое обследование, патогистологическое исследование материала, полученного при гистероскопии с раздельным диагностическим выскабливанием (1-я группа) и при аспирационной биопсии (2-я группа) с окраской срезов гематоксилином и эозином, по Маллори; иммуногистохимическая диагностика с оценкой рецептивности эндометрия к стероидным гормонам и гликоделину. С целью изучения местного иммунитета использовали антитела к CD4, СD8, CD20. Результаты. Среди 93 пациенток 1-й группы, поступивших в больницу с аномальным маточным кровотечением, у 52 (55,9%) диагностирован хронический эндометрит (ХЭ) на основании патоморфологического исследования материала после проведенного раздельного диагностического исследования. Из 105 пациенток 2-й группы ХЭ установлен у 59 (56,9%) после патоморфологического исследования. Среди репродуктивно значимых инфекций в анамнезе у пациенток с ХЭ выявлены: хламидиоз, трихомониаз, уреаплазмоз, микоплазмоз, генитальный герпес, цитомегаловирусная инфекция, папилломавирусная инфекция, генитальный кандидоз, бактериальный вагиноз. В группах с ХЭ в эндометрии отмечены нарушения функционального состояния железистого и поверхностного эпителия. В средней стадии фазы пролиферации экспрессия гликоделина в эпителиоцитах желез была обнаружена с интенсивностью от умеренной до сильной в 83,3%. Отсутствие секреции гликоделина в периовуляторном периоде является принципиально важным для регуляции репродуктивной функции, так как этот белок обладает контрацептивной активностью, блокируя связывание сперматозоидов с zona pellucida яйцеклетки. Соответственно выявленная продукция гликоделина в эндометрии в фазе пролиферации у пациенток с ХЭ может быть одним из патогенетических механизмов развития бесплодия. Кроме того, у пациенток 1-й и 2-й групп по сравнению с группой сравнения отмечено снижение уровня CD4 при одновременном повышении уровня экспрессии CD8 и снижении уровня CD20 особенно во 2-й группе. Заключение. У пациенток с ХЭ выявлена эндометриальная дисфункция, характеризующаяся снижением уровня рецепции к стероидным гормонам, нарушение секреции гликоделина, отставанием развития пиноподий и фазы менструального цикла, а также нарушением местного иммунитета. Вышеперечисленные изменения в эндометрии необходимо учитывать при прегравидарной подготовке у пациенток с ХЭ.

31 women suffered from chronic anemia who have wished to interrupt pregnancy in first trimester were investigated. We made the determination of placental (SP-I, β-hGC) and endometrial (glicodelin A, IGFBP-I) proteins concentration in serum, and exposed characteristics proteinsynthesizing function of chorion and endometrium.

The time course of morphofunctional changes in the liver, thymus, and spleen was observed in BALB/c mice with Con A-induced experimental hepatitis. The progress of alterative changes in the liver was paralleled by intensification of accidental involution of the thymus. On day 1 of hepatitis development high proliferative and cytostatic activity of splenocytes was paralleled by hemorrhagic necroses and depletion of the peri-arteriolar lymphoid sheaths in the spleen (T-zones), presumably due to migration of activated lymphocytes to the liver and barrier tissues. Later normalization of lymphocyte proliferative activity was paralleled by recovery and hyperplasia of the splenic T-cell zones.

An FAMG-Fertitest-M test-system for quantitation of fertility α2-microglobulin (FAMG) in biological fluids has been developed. It is based on original monoclonal antibodies against two different epitopes of FAMG. The range of FAMG concentrations reflecting thein vitro fertilizing capacity of sperm is determined, which allows one to assess the effectiveness of extracorporeal fertilization in the treatment of infertility.

Experiments on fibroblast-like Chinese hamster cells showed that agents inducing c-mitosis (colchicine, colcemid, low temperature) give rise to two distinct effects: stathmokinetic and radiomimetic. Toward the time of reversibility of the first of these effects, the second becomes clearly manifested as bridge formation. The appearance of this pathological form is evidently due to disturbance of cell nucleoprotein metabolism during c-mitosis.