Mass-spectrometric profiling of the serum in women at weeks 16-17 of gestation was carried out in order to detect proteomic predictors of preterm delivery. Changes in the production of 25 proteins (down-regulation for 13 proteins and up-regulation for 12 proteins) were detected in the sera of women whose pregnancies eventuated in premature deliveries. Among them, proteins with various regulatory functions were distinguished: antioxidant enzymes, chaperons, cytoskeleton proteins, cell adhesion molecules, and proteins involved in angiogenesis, proteolysis, transcription, inflammation processes, binding and transportation of various ligands. These results indicated the formation of proteomic imbalance as early as during trimester II, this eventually leading to premature delivery. The detected serum proteins were suggested as markers for early prediction of premature delivery.

The concentrations of vascular endothelial growth factor and endothelin in the placenta progressively increased during normal pregnancy. Production of vascular endothelial growth factor and endothelin in the placenta exceeded the normal during trimester I miscarriage and trimester III premature birth accompanied by intrauterine hypoxia. The concentration of these vasoactive substances during premature birth also increased in the umbilical cord. The compensatory decrease in the concentrations of vascular endothelial growth factor and endothelin in the placenta and umbilical cord was observed during full-term pregnancy with threatened abortion.

The content of the amino acids in the placenta during physiological pregnancy and fetal growth restriction (FGR) has been investigated my means of the method of ion-exchange chromatography. It has been found that in FGR the placental amino acid pool is characterized by a decreased content of arginine, proline, alanine, serine, cysteine, methionine, tryptophan, leucine, threonine, tyrosine, phenylalanine, glutamine and an increased content of dicarboxylic amino acids, lysine, histidine and glycine. These changes are accompanied by altered activity of some enzymes of amino acid metabolism, and the degree of these changes correlates with the level of corresponding amino acids.

The levels of zinc, copper, iron, and magnesium ions, and some of their binding proteins have been investigated in an amniotic fluid under the fetal growth retardation (FGR). FGR, developed under conditions of placental insufficiency, is characterized by a decrease in the content of zinc, iron, and magnesium ions and by an increase in the copper content in the amniotic fluid in the II and III trimesters of pregnancy. During these trimesters the levels of ceruloplasmin, ferritin, and Ca2+,Mg2+-ATPase were lower in FGR, while the level of zinc-a-2-glycoprotein was higher than during the same periods of normal pregnancy. Changes in the parameters studied in the amniotic fluid were associated with developmental disorders of the newborns. These changes obviously have a pathogenetic importance in the development of FGR, and the levels of metal ions and their ratio in the amniotic fluid can be used as markers of the pre- and postnatal pathology.

The content of amino acids — sources of gasotransmitters and the activity of enzymes of their metabolism have been studied in the placenta and amniotic fluid in full-term and complicated by preterm birth (PB). Determination of amino acids was carried out using an automatic analyzer; specific spectrophotometric methods were used to assess the activity of enzymes. The development of PB is accompanied by changes in the amino acid level already in the second trimester of pregnancy. Correlation of differently directions was found between the level of amino acids and the activity of the corresponding enzymes. The imbalance of amino acids in the fetoplacental system in PB is accompanied by a change in the production of their low molecular weight derivatives gas transmitters (NO, CO, H2S), which play an important role in the regulation of numerous metabolic processes.

No abstract

Analysis of the spectrum of amniotic fluid proteins in physiological and abnormal pregnancy using proteomic analysis allowed detection of a number of difference proteins, that are absent or, alternatively, appear in gestosis. Among absent proteins, there were NADPH-dependent carbonyl reductase, epidermal fatty acid-binding protein, haptoglobin, calgranulins A and B. In contrast to proteomic spectrum of amniotic fluid in physiological pregnancy, 7 new proteins appear during gestosis, 3 of them were identified: C area of immunoglobulin K-chain, breast cancer metastasis suppressor-1, and protein-1 containing AIG2-like domain. Possible effects of revealed differences in proteomic spectrum on development of main disturbances during gestosis are discussed. Difference proteins detected in amniotic fluid may serve as gestosis markers.

Протеомный анализ околоплодных вод, проведённый во II и III триместрах у женщин с физиологической беременностью и беременностью, осложнившейся плацентарной недостаточностью. Выявлены и идентифицированы белки отличия, отсутствующие при плацентарной недостаточности в указанные периоды гестации: пероксиредоксин-2, эпидермальный белок, связывающий жирные кислоты и гаптоглобин, а также белки, появившиеся при данной патологии и отсутствующие при физиологической беременности -гиппокальцин-подобный белок 1, CDC37-подобный белок, NKG2D лиганд 2, в III триместре -CDC37-подобный белок и NKG2D лиганд 2. Установленные различия в протеомном спектре околоплодных вод, очевидно, имеют патогенетическое значение в развитии плацентарной недостаточности. Обнаруженные белки отличия могут служить маркерами этой акушерской патологии.Ключевые слова: протеомный анализ, различие белковых паттернов, плацентарная недостаточность, околоплодные воды.ВВЕДЕНИЕ. Развитие гестации во многом зависит от метаболической полноценности плаценты, обеспечивающей нормальное функционирование биологической системы мать-плод на всем протяжении внутриутробного онтогенеза. Плацентарная недостаточность (ПН), являющаяся одной из основных причин перинатальной заболеваемости и смертности, характеризуется различными нарушениями метаболизма в этом органе [1][2][3]. Однако, несмотря на возросшее количество работ, посвященных проблеме данной акушерской патологии, вопросы молекулярных механизмов её развития еще далеки от разрешения.Принципиально новую информацию о ключевых аспектах формирования и прогрессирования осложнений беременности, в том числе и ПН, может дать использование современных медико-биологических технологий, получивших интенсивное развитие в течение двух последних десятилетий. К их числу относятся протеомные исследования, позволяющие оценить совокупность белков анализируемого объекта [4][5][6]. Ранее неизвестные сведения о белках тканей и биологических жидкостей не только углубят теоретические представления о путях развития патологического процесса, но и существенно повысят практические возможности его прогнозирования и ранней диагностики.Поскольку плацента является одним из главных источников белков околоплодных вод [7], протеомный анализ последних может дать представление 616 * -адресат для переписки