Yulia Milyutina

• Research Institute of Obstetrics and Gynecology named after D.O. Ott

BACKGROUND: Autophagy is essential for placenta formation and fetal brain development. Maternal hyperhomocysteinemia is a risk factor for pregnancy complications and may affect autophagy processes. However, the dynamics of autophagy markers are not studied enough so far. AIM: The aim of this study was to assess the dynamics of key autophagy markers...

Natural killer (NK) cells are a population of innate immune cells that have cytotoxic functions and are involved in protecting the body from viruses and transformed cells. Placental development is determined largely by the interaction of decidual NK cells and trophoblast cells. During pregnancy, NK cells accumulate around trophoblast cells, while r...

Introduction. Currently, folic acid preparations are administered during preconception period in an empirical manner. Along with synthetic folic acid, there also exists its reduced counterpart 5-methyltetrahydrofolate (5-MTHF). Manufacturers of the latter claim that 5-MTHF overcomes metabolic defects due to c.665C>T gene polymorphism in the methyle...

Natural killer (NK) cells are a population of innate immune cells that have cytotoxic functions and are involved in protecting the body from viruses and transformed cells. Placental development is largely determined by the interaction of decidual NK cells and trophoblast cells. During pregnancy, NK cells accumulate around trophoblast cells, while r...

Background Despite enormous advances in diabetes treatment, women with type 1 diabetes mellitus (DM) still experience delayed menarche, menstrual irregularities, fewer pregnancies, and a higher rate of stillbirths compared to women without the disease. Due to the fact that type 1 DM occurs at a young age, the preservation of reproductive health is...

BACKGROUND: The growth of neurological and mental diseases in the offspring of patients with pre- and gestational diabetes mellitus determines the need to study the regulatory function of the serotoninergic system of the brain in newborns. This plays a key role in its morphofunctional development in early ontogenesis, which is necessary for timely...

According to modern concepts, the susceptibility to certain diseases, especially to cognitive and neuropsychiatric disorders, can be formed during the period of embryonic development. Adverse factors that affect the mother during pregnancy increase the risk of the pathology development in the postnatal period. Despite the relationship found between...

Numerous studies have shown that various adverse factors of different nature and action mechanisms have similar negative influence on placental angiogenesis, resulting in insufficiency of placental blood supply. One of the risk factors for pregnancy complications with placental etiology is an increased level of homocysteine in the blood of pregnant...

The interaction of natural killer (NK) and trophoblast cells underlies the formation of immune tolerance in the mother–fetus system and the maintenance of the physiological course of pregnancy. In addition, NK cells affect the function of trophoblast cells, interacting with them via the receptor apparatus and through the production of cytokines. Mi...

BACKGROUND: The high frequency of neurological and mental diseases in children who had intrauterine retardatiojn development indicates the need to study specific markers of disorders of fetal brain functional development, in particular, the state of the serotonergic system, which plays a key role in the morpho-functional development of the brain in...

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 exp...

Maternal hyperhomocysteinemia causes the disruption of placental blood flow and can lead to serious disturbances in the formation of the offspring’s brain. In the present study, the effects of prenatal hyperhomocysteinemia (PHHC) on the neuronal migration, neural tissue maturation, and the expression of signaling molecules in the rat fetal brain we...

Intercellular communication plays a huge role in the vital activity of living organisms. At present, far less studied is distant cellular communication, in which, along with autocrine and paracrine regulations by soluble factors (e.g. cytokines and growth factors), of particular interest is communication by means of microparticles via their ligand-...

У самок крыс, находящихся на стадии проэструса, в условиях длительного потребления метионина были изучены уровни содержания норадреналина (НА) и дофамина (ДА) в зонах гипоталамуса, в которых происходят процессы синтеза (медиальная преоптическая область - МПО) и секреции гонадолиберина (срединное возвышение с аркуатными ядрами - СВ-Арк). Установлено...

Accumulation of the amino acid homocysteine in the mother’s body, known as hyperhomocysteinemia, is observed when there is an unbalanced diet during pregnancy, a lack of some vitamins, and genetic defects in methionine cycle enzymes. This increases the risk of microthrombosis in the placenta and developmental delay of brain tissue, neuronal death,...

SARS-CoV-2 negatively affects semen characteristics, impairs various biochemical processes in seminal fluid and within spermatogenic cells ultimately leading to male fertility decline. However, the distinct mechanisms, in particular, the role of oxidative stress on the consequences of coronavirus infection, have not been well investigated, which is...

Objective: To analyze glucose variability and investigate its role as a predictor for preeclampsia development in pregnant women with type 1 diabetes mellitus (T1DM) with various insulin therapy regimens. Methods: A total of 200 pregnant women with T1DM were included in the study. A hundred women used continuous subcutaneous insulin infusion (CS...

Microvesicles (MVs) are plasma extracellular vesicles ranging from 100 (150) to 1000 nm in diameter. These are generally produced by different cells through their vital activity and are a source of various protein and non-protein molecules. It is assumed that MVs can mediate intercellular communication and modulate cell functions. The interaction b...

Maternal hyperhomocysteinemia is one of the common complications of pregnancy that causes offspring cognitive deficits during postnatal development. In this study, we investigated the effect of prenatal hyperhomocysteinemia (PHHC) on inflammatory, glial activation, and neuronal cell death markers in the hippocampus of infant rats. Female Wistar rat...

BACKGROUND: Despite numerous studies, the etiopathogenesis of preterm birth in multiple pregnancy remains unclear, which determines the low effectiveness of measures for the prevention of preterm birth. This fact makes it necessary to study possible ways of implementing preterm birth in multiple pregnancies and to search for new biomarkers of their...

The article presents current views on maternal hyperhomocysteinemia (HHcy) as an important factor causing prenatal stress and impaired nervous system development in fetuses and newborns in early ontogenesis, as well as complications in adulthood. Experimental data demonstrate that prenatal HHcy (PHHcy) affects the morphological maturation of the br...

Monocytes\macrophages regulate angiogenesis via cytokine production and contact interactions with endothelial cells (ECs). The biological effects of macrophage-derived microvesicles (MVs) are studied using cell lines, such as monocytic leukemia THP-1 cell line. The effect of MVs produced by THP-1 cells on EC phenotype and functions remain understud...

Extracellular vesicles that are shed from the plasma membranes take an active part in intercellular communication, transporting a wide range of molecules, including proteins, lipids, nucleic acids and carbohydrates, being of great functional importance. One of the steps to better understanding of distant communications of cells and their regulatory...

Relevance: The growth of neuropsychiatric diseases caused by perinatal pathology indicates the need to study the biochemical markers of brain damage in the newborn for the timely prevention of adverse consequences. Serotonin in early ontogenesis provides intensive development of neuronal structures and cortical networks involved in the mechanisms o...

Hypothesis/aims of study. To date, one of the most important avenues of research in the field of reproductive medicine is the searching for new biochemical markers of oocyte quality and the prediction of the effectiveness of in vitro fertilization (IVF) protocols. The aim of this study was to assess the effect of relaxin levels in blood serum and f...

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),...

Microvesicles (MVs) are small (100-1000 nm) subcellular structures produced by both motionless and activated cells that can transfer molecules to target cells, and regulate physiological and pathological processes. MVs of leukocyte origin, in particular those produced by natural killer cells (NK cells), remain the least studied population of MVs. N...

Natural killer (NK) cells are the main population of leukocytes in decidua during the first trimester of pregnancy. NK cells can have contact with trophoblast cells during pregnancy, which raises the possibility of mutual influence. This research aimed to evaluate the proliferation and phenotype of peripheral blood NK cells in the presence of troph...

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...

BACKGROUND: Patients with any form of diabetes during pregnancy should achieve the target (close to physiological) values of glycaemia, the main condition for a safe course and outcomes of pregnancy. To accomplish this task, effective and safe methods of insulin therapy should be selected. AIM: To determine the glycaemic profile and pregnancy outco...

An essential aspect of metabolic imbalance of L-homocysteine and its accumulation in blood (hyperhomocysteinemia) is its aggravating effect in pregnancy. However, little is known about the effects of maternal increased L-homocysteine levels on brain development of fetuses. In the development of the fetus, accompanied by changes in metabolism in the...

Natural killer (NK) cells are of special interest among a multitude of microvesicle (MV) source cells. NK cells are a lymphocyte subpopulation performing contact cytolysis of virus-infected cells and tumor cells. Each of the NK cell populations has a unique receptor repertoire on its surface and, thus, unique functions. During their contact with a...

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...

This review article focuses on modern ideas about the role of neurotrophic factors (BDNF, NGF, NRG1, etc.) in the formation of the placenta and their impact on the development of the fetal nervous system in early ontogenesis. Data on the common effect of neurotrophic factors with vascular endothelial growth factor and metalloproteinases on angiogen...

Neuron-specific enolase (NSE) and brain-derived neurotrophic factor (BDNF) levels in umbilical cord blood in full-term newborns with asymmetrical intrauterine growth retardation resulted from chronic placental insufficiency have been studied. Not only a 2.0–2.5-fold increase in the blood NSE level, but also a reduction in BDNF levels were observed,...

Membrane extracellular microvesicles serve as carriers of a wide range of molecules, the most important among these are proteins, lipids, and nucleic acids. Cytotoxic proteins of natural killer cells play a key role in the realization of their cytolytic functions. An important stage in understanding of the distant communication of cells and mechani...

We analyzed the contents of neurotrophic factors (BDNF and NGF) and the S-100 protein in the hippocampus, cortex, and cerebellum of the rat brain during early postnatal ontogeny. We found that the BDNF content in the cortex is significantly lower than in the hippocampus and cerebellum, which may indicate a different degree of maturity of the studie...

Experimental hyperhomocysteinemia (HHC) induced in pregnant rats by L-methionine administration was shown to result in an increased content of caspase-3, as well as of a neurotrophic factor neuregulin (NRG1) and of a vesicular monoamine transporter 2 (VMAT2) in the fetal brain tissue analyzed on the 20th day of gestation (E20) while there were no s...

We evaluated the long-term neurophysiological effects of prenatal hyperhomocysteinemia (HHC) in mature female rats whose mothers received an oral methionine load daily from the fourth day of pregnancy to delivery. We have shown that after the experimentally induced prenatal HHC in mature female rats, shortterm and long-term memory were disrupted. T...

Effects of prenatal hyperhomocysteinemia on hypothalamic regulation of estrous cycles were studied in female rats. In mature rats exposed to prenatal hyperhomocysteinemia, changes in the catecholamine content in hypothalamic areas responsible for the formation of the preovulatory surge of gonadotropin-releasing hormone were revealed: the level of n...

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 pine...

The article presents a detailed analysis of correlations between the content of a variety of biogenic amines in the hypothalamic structures responsible for the gonadotropin-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...

The contents of neuron-specific enolase (NSE) and brain-derived neurotrophic factor (BDNF) was studied in the umbilical blood serum of healthy full-term newborns elective planned caesarean section and spontaneous delivery. The study has established that their levels in umbilical blood serum after elective planned caesarean section surgery are lover...

In recent years the study of age-related derangements of the gonadotropin releasing hormone (GnRH) synthesis and secretion resulting from both the GnRH gene expression changes and interaction of glia with GnRH-ergic neurons of the hypothalamus is a focus of attention. It was demonstrated earlier that this could result from the decreased activity of...

We studied the influence of hyperhomocysteinemia (HHC), which was induced in rats during pregnancy by a methionine load, on the indices of free-radical oxidation and antioxidant defense (AOD) in the brains of newborn pups. HHC in maternal body results in dysfunction of the endothelium, which plays an important role during the development of obstetr...

The data presented have shown the different effect of hyperhomocysteinemia (induced by 0,12-0,15 mg of methionine loading per os during 30 days) on monoamines content in hypothalamus and hippocampus of young (6-7 month) and old (20-22 month) female rats. It has been established that the level of catecholamines (noradrenaline, dopamine), 5 oxitrypta...

The effect of experimental hyperhomocysteinemia on diurnal dynamics of norepinephrine content in the medial preoptic area of the female rat hypothalamus, which is responsible for the synthesis of gonadotropin-releasing hormone (GnRH), has been studied. We investigated plausible neuroprotective effects of the pineal gland peptide pinealon (Glu-Asp-A...

Tobacco is an urgent problem in Russia and in the world. Recent years have seen increased prevalence of smoking among the population. Tobacco dependence is included in the international classification of diseases, the American Psychiatric Association. From habit associated increase in the frequency of chronic diseases, mortality. In Russia smokes a...

Possible neuroprotective effects of melatonin (pineal gland hormone) and epithalon (peptide preparation) on estrous cycles and the central part of the reproductive function regulation in female rats under the influence of unfavorable ecological factors were studied. Estrous cycles of young, mature, and aging rats exposed to light pollution were cha...

The role of folic acid and negative effects of its deficit in pregnancy are discussed. The folate content in the blood of pregnant women who were administered folic acid containing drugs were shown to excess the standard allowances. Possible side-effects of continuous folate blood level increase were revealed. The recommendations for folate therapy...

Tobacco smoking is one of the pressing issues of public health. Russia ranks among the countries with a very high smoking rate. Smoking frequency among pregnant women in St. Petersburg is about 26.4%, among which 18.9% of the women smoke every day, and the rest 7.5% of them on the occasion. Complications from pregnancy (threatening miscarriage, pre...

The age-related dynamics of 6-hydroxymelatonin sulfate (6-OHMS) excretion was studied in 175 patients with gastric (89 patients) and colorectal cancer (86 patients). An age-related decrease in 6-OHMS excretion and disturbances of its circadian rhythm were revealed. These changes were directly proportional to the prevalence of cancer and in the case...

Potential neuroprotective effects of the pineal gland hormone melatonin and peptide preparation epitalon on estrous cycles and the central regulation of reproduction in female rats exposed to unfavourable environmental factors have been studied. Estrous cycles of young, mature and aging rats exposed to light pollution were described. The diurnal dy...

Catecholamines play an important role in the hypothalamic regulation of the synthesis and secretion of gonadotropin-releasing hormone. 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 (D...

We reviewed experimental models in which an increase in the content of homocysteine in rat blood was achieved by chronic (1 month) consumption of methionine with drinking water (1 g/kg weight) or forced oral injection of methionine solution (0.1–0.15 g in a small volume of water). The effectiveness of the model of hyperhomocysteinemia was evaluated...

Our data on elucidation of the role of catecolaminergic systems of the hypothalamusin gonadotropin-releasing hormone (GnRH) pre-ovulatory surge formation in female ratsis presented in this study. It has been shown that diurnal variations of norepinephrine(NE) in the medial pre-optic area (MPA) and of dopamine (DA) in the median eminencewith arcuate...

We studied the effects of melatonin and epiphysis peptides (epithalamin and epitalon) on the daily dynamics of the content of noradrenalin (NA) in the medial preoptic area (MPA) and dopamine (DA) in the median eminence with the arcuate nuclei (ME-Arc), which was disturbed by a single injection of 1,2-dimethylhydrazine (DMH). We found that the admin...

Total monoamine oxidase activity in the medial preoptic area and median eminence (with surrounding tissue) has been studied in female rats of three age groups, viz., those aged 1.5–2 months (peripubertal), 4–5 months (mature), and over 12 months (aging). Monoamine oxidase activity was measured using kynuramine as a substrate and changes in the conc...