Disruptions in the reproductive system of female rats after prenatal lipopolysaccharide-induced immunological stress: role of sex steroids.

Stress signals during fetal or early postnatal periods may disorganize reproductive axis development at different levels. This study was aimed to test the hypothesis that prenatal immunological stress induced by bacterial endotoxin, lipopolysaccharide (LPS), has impact on structure and function of the reproductive system in female offspring. Adult female Wistar rats were divided into two groups, a control group (n = 5) and a LPS group (n = 12). Rats were injected with LPS 50 µg/kg body or 0.9% saline intraperitoneally on the 12th day of pregnancy. After birth the female pups (n = 20 in each group) were divided into four groups: (group 1) 0.9% saline prenatally, sesame oil (vehicle) postnatally; (group 2) LPS prenatally, sesame oil postnatally; (group 3) LPS prenatally, fulvestrant postnatally; (group 4) LPS prenatally, flutamide postnatally. Pups were injected subcutaneously into the neck with fulvestrant (estrogen receptor antagonist), 1.5 mg/kg in sesame oil, from postnatal day (PND) 5 to PND14; or flutamide (androgen receptor antagonist), 20 mg/kg in sesame oil, from PND14 to PND30. Rats of the control group were injected with sesame oil during the same time period. Parameters were evaluated by ELISA (serum estradiol and testosterone) and ovarian histology. The main findings were: (1) prenatal stress during the critical period resulted in delayed vaginal opening, decreased body weight and serum concentrations of sex steroids, and significant disorders in ovarian development; (2) postnatal estradiol and testosterone antagonist treatments decreased follicular atresia through increasing the number of healthy follicles and restored endogenous steroid production. Lay summaryImmunological stress, caused by simulating infection through exposure to a bacterial toxin (LPS), during a critical period of fetal development in laboratory rats results in delayed reproductive maturity, decreased body weight and decreased secretion of sex steroids in female offspring, and abnormalities in the ovaries like those in polycystic ovarian syndrome. These prenatally toxin-induced sexual disorders in females could be corrected by estradiol/testosterone antagonists during the postnatal period.

[About Development of Programs of Struggle with Tobacco Smoking in Medical Workers].

The article presents a review of prevalence of smoking among physicians and medical nurses suffering from nicotine dependence. The most of smoking medical workers began to smoke already during student years. they don't relate their diseases with smoking. The incomplete awareness of true causes of one's own diseases is manifested in ignoring preventive activities and healthy life-style. The actuality of necessity of development of program of prevention tobacco dependence in medical workers suffering from tobacco dependence is demonstrated.

The inhibition of dopamine synthesis in fetuses changes the pattern of T-lymphocyte maturation in the thymus of adult rats.

The mRNA for dopamine receptors of type D1, D3, D5, but not type D2, was detected in the thymus of rats starting from day 16 of embryonic development (E16). Dopamine at concentrations of 10-8-10‒6 M inhibited fetus thymocyte response to mitogen, confirming the functionality of the receptors and the possibility of a direct effect of dopamine on the developing thymus. Pharmacological inhibition of catecholamine synthesis in the crucial period of thymus development leads to long-term changes in the T-system immunity due to increased production of natural regulatory T-lymphocytes. The presence and functional activity of dopamine receptors in the fetal thymus indicates its ability to influence the development of the immune system of rats during ontogeny.

[Perinatal stress in brain programming and pathogenesis of psychoneurological disorders].

We analyzed data from our studies and other author's works concerning the influence of stress stimuli on the development of neuroendocrine and immune systems. The results of our analysis suggest that "immunological stress" induced by viral or bacterial infection, an unhealthy diet, and the mother's behavior during pregnancy and lactation are significant risk factors for the developing offspring. The brain is the key target for these factors. The continuous effect of stress stimuli during critical periods of brain development induces hyperactivity and increased response of hypothalamic-pituitary-adrenal system. This can increase the risk of the development of psychoneurological, metabolic, immunological, and behavioral disorders and the suppression of reproduction in the offspring. The plasticity of physiological systems helps the developing organism to adapt to the changing environment.

[Plasticity of neuroendocrine and immune systems in early development].

This article provides an analysis of our own and published data on the reciprocal morphogenetic influence of the neiuroendocriie and imnimune systems on their formation and function in mammals. It is substantiated that, in early ontogeny, neurohormones regulate the growth and differentiation of various tissues in the body, including the lymphoid tissue. Thymicpeptides, in turn, affect the development of the hypothalamic-pitiitary-adrenal and gonadal-systems. Various adverse factors and changes in the physiological concentrations of hormones in the critical periods of development of these systems change their functions, and the plasticity of physiological systems in early ontogeny allows the body to adapt to new conditions. Disturbances in the interaction of the neuroendocrineand immune systems in the perinatal period induce apredisposition to various diseases in progeny.

[Expression of the RT1A molecule of the class I major histocompatibility complex in a Walker 256 tumor after transplantation into Brattleboro rats with a genetic defect of arginine-vasopressin synthesis].

The dynamics of expression of the RT1A antigen of the class I major histocompatibility complex (MHC) in a Walker 256 tumor after its transplantation into Brattleboro rats with a genetic defect of Arginine-Vasopressin synthesis in the hypothalamus was studied. Expression of the RT1A antigen was detected by means of Western-blotting and flow cytometry in the tumor cells on the 14th-17th days after transplantation. In addition, a simultaneous increase in the portion of cells that express the RT1A antigen and in the level of its expression per cell was observed. It is presupposed that at a deficiency of Arginine-Vasopressin, a renewal of expression of the class I MHC antigens, which results in an increase of immunogenicity of this tumor and regression, occurs in the Walker 256 tumor in the Brattleboro rats.

[Specific features of the melanophore system in different color morphs of larvae of the common toad (Bufo bufo L.)].

In a natural pond among usual black larvae of the common toad (Bufo bufo L.), a few unusual individuals of red-olive coloring were found out. In both morphs we investigated the melanophores of skin using different methods. The ESR-spectrometric analysis has shown the absence of distinctions between morphs by the amount of melanin. Analysis of total preparations of skin has shown the presence of various kinds of melanophore cells both in the derma and in the epidermis. Among typical melanophores, essentially differing cells appeared (atypical cells). In black morph tadpoles, the number of all kinds of melanophores is significantly greater than in red-olive morphs. It is shown that dark coloring is connected with a considerable number of atypical cells in the epidermis imposed on a dense layer of typical dermal melanophores with dispersed melanin.

[The role of serotonin in the immune system development and functioning during ontogenesis].

In this study, we investigated the influence of serotonin on the development and functioning of T- and B-cell-mediated immunity during ontogenesis using the pharmacological model of serotonin depletion in rat fetuses. It has been demonstrated that prenatal serotonin deficiency resulted in a decrease in thymus and spleen weights, changes in their cellular composition, and long-lasting disturbances in cell-mediated and humoral immunity in postnatal ontogenesis. The data obtained suggest that serotonin may be considered a morphogenic factor in development of the immune system.

[Sleep disorders in nurses working during the COVID-19 pandemic]. / Rasstroistva sna u meditsinskikh sester, rabotayushchikh v period pandemii COVID-19.

The reorganization of treatment facilities during the COVID-19 pandemic has altered the working conditions of large numbers of the health workers (HW) worldwide. The implementation of professional activities in such realities has led to an increased risk of developing a number of psychological disorders, including insomnia. The percentage of insomnia in HW has increased significantly. The nurses were the most vulnerable, because they are women and they work in an understaffed environment. The influence of shift work and stress conditions on the risk of insomnia, methods of prevention and treatment of this disorder are thoroughly examined in the article.

[Effect of bacterial endotoxin on migration of gonadotropin-releasing, hormone producing neurons in rat embryogenesis].

The effect of bacterial lipopolysaccharide endotoxin (LPS), immune system activator, on differentiation and migration of gonadotropin-releasing, hormone producing neurons in rat embryogenesis has been studied. Intraperitoneal introduction of LPS (18 jg/kg) to pregnant rats on the 12th day of pregnancy led to 50% decrease in total number of GRH-neurons in the forebrain of 17-day-old embryos and 17% decrease in 19-day-old embryos. At the same time, the number of GRH-neurons in the nasal area of the head of 17- and 19-day-old embryos increased by 40 and 50%, respectively, whereas it increased by 20% in olfactory bulbs of 17-day-old embryos and did not changed in olfactory bulbs of 19-day-old embryos. Neither the total number of neurons nor their distribution patterns were affected by the introduction of LPS into pregnant rats on the 15th day of pregnancy. Singular localization of GRH-neurons in embryo forebrain was observed after LPS administration, whereas the neurons were located by groups of 3-4 cells in rostral areas. Therefore, at the early stages of pregnancy, LPS was shown to suppress initial stages of differentiation and migration of GRH producing neurons. The effects observed in our study may be mediated by LPS-induced, proinflammatory cytokines.

[Reparative regeneration of rat skin under influence of hollow cathode lamp (HCL) with manganese and copper line spectrum emission].

Influence of local light exposure by hollow cathode lamp with typical manganese and copper (HCL-Mn, Cu) line emission spectrum on posttraumatic regeneration rate of rat skin has been investigated. We performed the comparative analysis of the morphology and the differentiation ability of rat skin on the 15th and 24th days after full-thickness skin wound had been inflicted on rat dorsums. On the 15th day after injury, the experimental group (daily 30 s exposure for two weeks) showed scab loss, re-epithelialization, and hair regrowth, in contrast to the control rats, where scabs were still observed on the 24th day. Histological analysis revealed that in contrast to the control group the treatment with HCL-Mn, Cu resulted in the increased number of hair follicles and sebaceous glands, the decreased number of blood vessels and horizontal orientation of collagen fibers. The immunohistochemistry for OX-62 revealed that the number of dermal dendritic cells in the experimental groups was maximal on the 15th day, and then decreased to the 24th day after injury. The number of dermal dendritic cells was significantly lower in the control group. The immunohistochemistry for pan-keratins in the control animals revealed a high number of cells expressing different types of keratins, distributed in the main part of the epidermis on the 15th day after surgery, whereas in the experimental group the number of such cells was significantly lower and the cells were concentrated more close to the external part of the epidermis. The number of cells stained for keratin 19 was higher in the experimental group on the 15th day after surgery, whereas this number decreased in this group on the 24th day after surgery as compared to the control group. Thus, typical manganese and copper line spectrum emission emitted by hollow cathode lamp stimulates innate immunity, accelerates restoration of derma, skin epithelium and other skin derivates, and stimulates wound healing in general.

[Cross-regulation in development of neuroendocrine and immune systems].

Cross-regulatory effects of immune and neuroendocrine systems on their appearance and functioning occur during a whole life period. At different stages of ontogenesis, the functions of these systems are diverse. In perinatal ontogenesis hormones, neuropeptides and neurotransmitters control the processes of growth and differentiation of various embryo tissues, particularly lymphoid. In the postnatal period, their functions are mostly in homeostasis maintaining of the immune system in response to changes of the environment. Conversely, transmitters of the immune system, such as cytokines, whose synthesis is increased in inflammation, and thymic peptides, program the development of the neuroendocrine system of the embryo. The perinatal period is crucial for final appearance of these systems. Changes in one of the interacting systems, caused by negative environmental factors at this stage, usually provoke changes in other developing systems for a long period. Plasticity of physiological systems in perinatal development allows the organism to adapt to changed conditions. However, these changes can limit physiological functions in interacting systems and induce the appearance of various pathologies in postnatal life.

[Mechanisms of the hypothalamic-pituitary and immune system regulation: the role of gonadotropin-releasing hormone and immune mediators].

Different aspects of the reciprocal regulatory influence of systems producing the immune and gonadotropin-releasing hormone (GnRH) in pre- and postnatal ontogeny are discussed in this review. GnRH is a neurohormone synthesized by a small population of neurons located in the anterior hypothalamus, which regulates the secretion of gonadotropines in the anterior lobe of the pituitary gland and they finally regulate the synthesis of sex steroids. Particular attention is given to analysis of the data involving the role of thymus peptides and cytokines in GnRH-system regulation in the normal condition and in the case of inflammation development caused by endotoxines in adult animals. The main prospects of the studies involving the influence of proinflammatory cytokines on GnRH-neuron migration and differentiation in prenatal ontogenesis are also discussed.

[Evolution of adaptive immunity].

The current state of the problem of emergence and evolution of adaptive immunity in different taxonomic groups of animals is analyzed. Special attention is given to the emergence and phylogenetic development of the lymphocyte, the key component of immune response, as well as to the evolutionary development of T- and B-cell immune systems, adaptive immune responses and their molecular regulators (cytokines), and antigen-recognition structures.

[Immune proteasomes in the developing rat spleen].

Changes in the structure of the rat spleen and the distribution of immune proteasomes in it during early postnatal development have been studied using double immunofluorescent staining of tissue sections with antibodies to the LMP7 immune proteasome subunit and to specific markers of T and B lymphocytes. It has been shown that the white pulp on postnatal day 5 is not yet colonized by lymphocytes and contains a smaller amount of immune proteasomes than the red pulp. At this stage, T and B lymphocytes concentrate mainly in the red pulp. On day 8, B lymphocytes occupy the marginal zone, while T lymphocytes aggregate into dense strands close to the white pulp. By day 18, T lymphocytes form periarteriolar sheaths in the white pulp, and the contents of immune proteasomes in the red and white pulp become equally high. An increase in the total content of immune proteasomes in the spleen on the third postnatal week was revealed in our previous study by Western blotting. In addition to T and B lymphocytes, immune proteasomes have also been revealed in other spleen cell types, probably in macrophages and reticular cells of the white pulp. Thus, the postnatal development of the spleen is associated with an increase in the contents of immune proteasomes in it.