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.

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.

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.

[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.

[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.

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.

Expression of VEGF and VEGF-R3 receptor by placental endothelial cells in health and gestosis.

We carried out a comparative analysis of changes in VEGF secretion and expression of VEGF-R3 receptor by placental endothelial cells in health and gestosis and of changes in VEGF-R3 expression by EA.hy926 human endothelial cells during culturing with supernatants conditioned by placental explants from women with normal pregnancy and patients with gestosis. Reduced secretion of VEGF and expression of VEGF-R3 by placental endothelial cells in gestosis can be caused by functional deficiency of the endothelial cells and low viability of endothelial cells.

Contractile activity of rabbit uterus at the end of pregnancy and a method for its registration.

We developed a method for synchronous registration of electrical activity of the myometrium in pregnant rabbit females and electrocardiograms of the female and fetus on a paper tape and on PC in the online mode using an original pickup for registration of intrauterine pressure in awaken animals in a natural (sitting) posture. The method causes no pregnancy complications and is adequate for evaluation of uterine contractility, female and fetal status in different variants of the experiment.

Comparative efficiency of intraperitoneal interleukine-2 and interferon-A in rats with experimental endometriosis.

Intraperitoneal injection of rat IFN-alpha and human IL-2 to rats with experimental endometriosis led to complete regression of endometrioid heterotopies in 50 and 60% cases, respectively. Retention of the endometrioid epithelium resulted in a significant reduction of proliferative activity of its cells, degree of vascularization, and number of macrophages in the leukocytic infiltration of endometrioid heterotopies.

Spontaneous and LPS-induced secretion of cytokines by villous chorion tissue.

Secretion of IL-1alpha, IL-1beta, IL-6, IL-10, and TNF-alpha cytokines by villous chorion cultures (7-14 weeks) during normal pregnancy and in spontaneous abortions was studied. Secretion of IL-1alpha and IL-6 increased 4.5 and 7.

Study of cytokine profile and angiogenic potential of peritoneal fluid in patients with external genital endometriosis.

The concentrations of proinflammatory cytokines (IL-1beta, IL-6), vascular endothelium growth factor, tumor growth factor-beta, and insulin-like growth factor-1 were measured in the peritoneal fluid of patients with external genital endometriosis and healthy women by enzyme immunoassay. The effect of peritoneal fluid from patients with external genital endometriosis on proliferative activity of EA.Hy926 human endothelial cells was evaluated by the method based on the analysis of cell cycle by flow cytometry.

Local production of interleukins and growth factors in external genital endometriosis.

Secretion of some IL and growth factors (VEGF, IGF-I, TGFbeta) by endometrial tissues and endometrioid heterotopies was studied in vitro in patients with external genital endometriosis of different severity. The production of IL-1beta, IL-2, IL-6, and VEGF in the endometrium increased in severe external genital endometriosis, while the secretion of TGFbeta decreased; hyperproduction of IL-2, IL-6, VEGF and decreased production of TGFbeta were detected in endometrioid foci. Presumably, local cytokine imbalance and increased proliferative activity of endometrial cells are involved in the mechanisms of formation and functioning of endometrioid foci.

Secretion of proinflammatory cytokines by villous chorion tissue in spontaneous abortion.

Secretion of proinflammatory cytokines IL-1 beta, TNF-alpha, IL-6, IFN-alpha, and IFN-gamma by the chorion tissue (8-12 weeks) was studied in normal gestation and spontaneous abortion. The production of IL-1 beta, TNF-alpha, and IFN-alpha virtually did not change in spontaneous abortion, while IFN-gamma was not secreted in all experimental groups. The production of IL-6 increased more than 2-fold in patients with spontaneous abortion during the first trimester.