Neurotrophins: are they involved in immune tolerance in pregnancy?

In this review, an attempt was made to substantiate the possibility for neurotrophins to be involved in the development of immune tolerance based on data accumulated on neurotrophin content and receptor expression in the trophoblast and immune cells, in particular, in natural killer cells. Numerous research results are reviewed to show that the expression and localization of neurotrophins along with their high-affinity tyrosine kinase receptors and low-affinity p75NTR receptor in the mother-placenta-fetus system indicate the important role of neurotrophins as binding molecules in regulating the crosstalk between the nervous, endocrine, and immune systems in pregnancy. An imbalance between these systems can occur with tumor growth and pathological processes observed in pregnancy complications and fetal development anomalies.

The Role of Cytokines in Maintaining the Dynamics of Cell-Cell Interaction between Natural Killer Cells and Trophoblast Cells.

We analyzed the effect of individual cytokines that are secretory products of placenta typical of the uteroplacental bed. The proinflammatory cytokines IL-6, IFNγ, and IL-1β increased the expression of TGFβR2 molecule by trophoblast cells, while VEGF and PLGF increased the expression of CD45, CD29, and CD54 adhesion molecule by trophoblast cells. The antiinflammatory cytokine IL-4 increased LeptinR expression by trophoblast cells.

[Antioxidative properties of geroprotective peptides.].

The results of studies on the antioxidant effect of a number of peptide drugs, which is manifested at various levels, ranging from cells to the whole body, in adulthood and during aging, under the influence of extreme environmental factors, indicate the important role of low-molecular peptides in the mechanisms of regulating homeostasis during aging. The antioxidant properties of regulatory peptides are shown in experiments both on intact sexually mature animals, and especially clearly during aging or the action of extreme environmental factors (hypoxia, hypokinesia). A number of the studied substances (AEDG, KE) have a membrane-stabilizing effect, preventing osmotic and acid hemolysis of red blood cells and reducing the level of extra-erythrocyte hemoglobin and total peroxidase activity in blood plasma.

"All-In-One" Genetic Tool Assessing Endometrial Receptivity for Personalized Screening of Female Sex Steroid Hormones.

Endometrium is the uterine lining that undergoes hundreds of cycles of proliferation, differentiation, and desquamation throughout a woman's reproductive life. Recently, much attention is paid to the appropriate endometrial functioning, as decreased endometrial receptivity is stated to be one of the concerns heavily influencing successes of embryo implantation rates and the efficacy of fertilization (IVF) treatment. In order to acquire and maintain the desired endometrial receptivity during IVF cycles, luteal phase support by various progestagens or other hormonal combinations is generally recommended.

Maternal Hyperhomocysteinemia Induces Neuroinflammation and Neuronal Death in the Rat Offspring Cortex.

Maternal hyperhomocysteinemia is one of the common complications of pregnancy that causes offspring cognitive deficits during postnatal development. In the present work, we evaluated the effect of prenatal hyperhomocysteinemia on structural and ultrastructural organization, neuronal and glial cell number, apoptosis (caspase-3 content and activity), inflammatory markers (tumor necrosis factor-α, interleukin-6, and interleukin-1β), and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation in the offspring brain cortex in early ontogenesis. Wistar female rats received methionine (0.

Neurotrophins of the Fetal Brain and Placenta in Prenatal Hyperhomocysteinemia.

Prenatal hyperhomocysteinemia (PHHC) in pregnant rats was induced by chronic L-methionine loading, resulting in a significant increase in the L-homocysteine content both in the mothers' blood and blood and brain of fetuses. Significant decrease in the weight of the placenta, fetus, and fetal brain was detected by the morphometric studies on day 20 of pregnancy. PHHC also activated maternal immune system due to the increase in the content of proinflammatory interleukin-1β in the rat blood and fetal part of the placenta.

Placental protein expression of kisspeptin-1 (KISS1) and the kisspeptin-1 receptor (KISS1R) in pregnancy complicated by diabetes mellitus or preeclampsia.

Purpose: Kisspeptins regulate the trophoblast invasion. The disturbance of this process might lead to the development of preeclampsia (PE). Diabetes mellitus (DM) is associated with the high rate of this complication.

Role of Caspases in the Cytotoxicity of NK-92 Cells in Various Models of Coculturing with Trophoblasts.

Studies of interactions between natural killer (NK) cells and trophoblasts and identification of conditions for the NK cells to perform their cytotoxic function are of fundamental and practical importance for understanding their role in the development of pathological processes and complications during pregnancy. In this study, we examined changes in the content of caspases and studied activation of these enzymes in Jeg-3 trophoblasts in various models of their coculturing with NK-92 cells and demonstrated the necessity of direct contact between these cell populations for the activation of caspase-8 and caspase-3 in the trophoblasts. Contact coculturing of the two cell lines resulted in the appearance of the cytotoxic protein granzyme B in Jeg-3 cells that was accompanied by a decrease in the content of this enzyme in NK-92 cells.

Antibody to Marinobufagenin Reverses Placenta-Induced Fibrosis of Umbilical Arteries in Preeclampsia.

Background: Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). Immunoneutralization of heightened MBG by Digibind, a digoxin antibody, reduces blood pressure (BP) in patients with PE, and anti-MBG monoclonal antibody lessens BP in a rat model of PE. Recently, we demonstrated that MBG induces fibrosis in cardiovascular tissues via a mechanism involving inhibition of Fli-1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis.

Pathogenomics of Endometriosis Development.

For over 100 years, endometriosis, as a chronic, estrogen-dependent, inflammatory, heritable disease affecting approximately 5⁻10% of women in reproductive age has been the focus of clinicians and scientists. In spite of numerous environmental, genetic, epigenetic, endocrine, and immunological studies, our knowledge of endometriosis is still fragmentary, and its precise pathophysiology and pathogenomics remain a mystery. The implementation of new technologies has provided tremendous progress in understanding the many intrinsic molecular mechanisms in the development of endometriosis, with progenitor and stem cells (SCs) of the eutopic endometrium as the starting players and endometriotic lesions as the final pathomorphological trait.

Reciprocal Interactions of Mitochondria and the Neuroimmunoendocrine System in Neurodegenerative Disorders: An Important Role for Melatonin Regulation.

Structural and functional alterations of mitochondria are intimately linked to a wide array of medical conditions. Many factors are involved in the regulation of mitochondrial function, including cytokines, chaperones, chemokines, neurosteroids, and ubiquitins. The role of diffusely located cells of the neuroendocrine system, including biogenic amines and peptide hormones, in the management of mitochondrial function, as well as the role of altered mitochondrial function in the regulation of these cells and system, is an area of intense investigation.

[On the discontinuity of the annuity curves in Drosophila melanogaster Canton-S strain. IV. Effect of low temperature on the early imaginal stage].

We tested the effect of low temperature (18-20 °C) applied at the 13-22 days of imago life. We detected prolongation of individual life span. The effect is due to prolongation of the first phase of the annuity curve and thus to further delay of the next ones.

[Melatonin as a marker of the grade of cardiac disorders during cachexia development in oncological patients of different ages].

We have examined 103 patients at the age from 28 to 78 with the newly diagnosed oncological disease at stages II-IV before the beginning of anticancer treatment. The identification of the signs of the cachexia syndrome and its stage (pre-cachexia, cachexia) were carried out in the accordance with the CASCO criteria (2011) and taking into the account the age of the patients. The cardiovascular infringements were found to be comorbid to the oncological disease significantly more often in patients with signs of cachexia syndrome on the pre-cachexia stage and the total index of cardiovascular disorders in oncological patients increases with the severity of cachexia.

Role of Reactive Oxygen Species in Premature Ageing of the Female Reproductive Function.

Industrial xenobitics, as well as endogenous damaging factors, such as L-homocysteine, are a well-known source of reactive oxygen species that disrupt biological processes. Among many others, luteinizing hormone releasing hormone synthesis and secretion mediated by a variety of neurotransmitters, which are under control of the hypothalamus and pineal gland, may be put in peril by reactive oxygen species. Their formation can be one of the reasons for the reproductive function shutdown in ageing as the generic response to the damaging factors independent of their nature.

Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging.

Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin А); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland.

[Age-related changes in biogenic amine content and oxidative stress profile in the rat hypothalamus in hyperhomocysteinemia].

The article presents a detailed analysis of correlations between the content of a variety of biogenic amines in the hypothalamic structures responsible for the luteinizing hormone releasing hormone synthesis and secretion (the medial preoptic area and median eminence) and such independent factors as total L-homocysteine plasma level elevation induced by L-methionine loading and aging. Both a nature and a pattern of changes in oxidative stress profile were evaluated. It was shown that ageing, when compared to hyperhomocysteinemia, is a determining factor influencing biogenic amine content in the studied hypothalamic structures.

Effects of placental tissue secretory products on the formation of vascular tubules by EA.Hy926 endothelial cells.

The formation of vascular tubules by EA.Hy926 endothelial cells was studied in the presence of placental secretory products from women with normal gestation at early and late periods and with gestosis. The factors secreted by placental tissues at the early stages of placental development stimulated the branching angiogenesis, while the products of the end of pregnancy stimulated nonbranching angiogenesis.

Phenotypical characteristics of peripheral blood monocytes in normal pregnancy and gestosis.

Monocyte migration from the peripheral blood to the uterine decidual tissue is essential for the regulation of placental development. We evaluated the phenotypical changes in the peripheral blood monocytes in pregnant women. The peripheral blood counts of monocytes expressing CD11b, CD47, and integrin β7 were elevated in women with normal gestation in comparison with nonpregnant women; the intensity of CD62P, CD11b, CD11c, CD29, CD31, and CD54 expression was higher in pregnancy.

Effects of placental secretory factors on cytokine production by endothelial cells.

We studied the effects of soluble products of the placental tissue from women with normal pregnancy and gestosis on the cytokine secretion by endothelial EA.Hy926 cells. The secretory products of the placental tissue induced the production of angiogenin, bFGF, IL-8, MCP-1, and RANTES by endothelial cells.

Melatonin and pineal gland peptides are able to correct the impairment of reproductive cycles in rats.

Catecholamines play an important role in the hypothalamic regulation of the synthesis and secretion of gonadotropin- releasing hormone, or gonadoliberin. We have shown that melatonin and the pineal gland peptides (epithalamine and epitalon) exert a correcting influence on the diurnal dynamics of norepinephrine (NE) in the medial preoptic area (MPA) and of dopamine (DA) in the median eminence with arcuate nuclei (ME-Arc) disturbed by single administration of the neurotoxic xenobiotic 1,2-dimethylhydrazine (DMH) in female rats. It has been found that experiments with DMH administration can be used as an animal model of female reproductive system premature aging.

In vitro expression of vascular endothelial growth factor and its receptors by placental macrophages.

The expression of VEGF and membrane-bound and soluble forms of the VEGF-R1 receptor in cultured placental macrophages (trimesters I and III of pregnancy) was studied by flow cytometry, cytometric bead array, and ELISA. Nearly all population of placental macrophages (98%) was capable of producing VEGF during the early and late gestational periods. However, the expression of cellular VEGF-R1 varied from 3.

Expression of thrombospondin-1 gene mRNA and protein in the placenta in gestosis.

The expression of TSP-1 gene mRNA and TSP-1 protein in the placental tissue was studied during normal pregnancy and in gestosis. The formation of placental tissue in normal gestation was associated with expression of TSP-1 gene mRNA and of TSP-1 protein. Gestosis was associated with inflammatory reaction in the placenta characterized by increased counts of lymphocytes and macrophages in the villous stroma and involution degenerative changes in tissue.

Regulatory mechanisms for apoptosis in placental tissue during normal pregnancy and gestosis-complicated pregnancy.

The localization of apoptosis and expression of proapoptotic and antiapoptotic factors by the placental tissue were compared during normal pregnancy and gestosis-complicated pregnancy. The degree of apoptosis did not differ in the third trimester of normal pregnancy and gestosis-complicated pregnancy. Increased expression of Fas, caspase-8, and caspase-3 in placental tissue during normal pregnancy was shown to contribute to the suppression of angiogenesis and growth of placental tissue.