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  1. Article ; Online: Reference Gene Validation in the Embryonic and Postnatal Brain in the Rat Hyperhomocysteinemia Model.

    Kovalenko, Anna A / Schwarz, Alexander P / Shcherbitskaia, Anastasiia D / Mikhel, Anastasiia V / Vasilev, Dmitrii S / Arutjunyan, Alexander V

    Neurotoxicity research

    2024  Volume 42, Issue 2, Page(s) 19

    Abstract: Maternal hyperhomocysteinemia (HCY) induced by genetic defects in methionine cycle enzymes or vitamin imbalance is known to be a pathologic factor that can impair embryonal brain development and cause long-term consequences in the postnatal brain ... ...

    Abstract Maternal hyperhomocysteinemia (HCY) induced by genetic defects in methionine cycle enzymes or vitamin imbalance is known to be a pathologic factor that can impair embryonal brain development and cause long-term consequences in the postnatal brain development as well as changes in the expression of neuronal genes. Studies of the gene expression on this model requires the selection of optimal housekeeping genes. This work aimed to analyze the expression stability of housekeeping genes in offspring brain. Pregnant female Wistar rats were treated daily with a 0.15% L-methionine solution in the period starting on the 4th day of pregnancy until delivery, to cause the increase in the homocysteine level in fetus blood and brain. Housekeeping gene expression was assessed by RT-qPCR on whole embryonic brain and selected rat brain areas at P20 and P90. The amplification curves were analyzed, and raw means Cq data were imported to the RefFinder online tool to assess the reference genes stability. Most of the analyzed genes showed high stability of mRNA expression in the fetal brain at both periods of analysis (E14 and E20). However, the most stably expressed genes at different age points differed. Actb, Ppia, Rpl13a are the most stably expressed on E14, Ywhaz, Pgk1, Hprt1 - on E20 and P20, Hprt1, Actb, and Pgk1 - on P90. Gapdh gene used as a reference in various studies demonstrates high stability only in the hippocampus and cannot be recommended as the optimal reference gene on HCY model. Hprt1 and Pgk1 genes were found to be the most stably expressed in the brain of rat subjected to HCY. These two genes showed high stability in the brain on E20 and in various areas of the brain on the P20 and P90. On E14, the preferred genes for normalization are Actb, Ppia, Rpl13a.
    MeSH term(s) Female ; Pregnancy ; Rats ; Animals ; Hyperhomocysteinemia/chemically induced ; Hyperhomocysteinemia/genetics ; Rats, Wistar ; Brain ; Methionine ; Racemethionine ; Hypoxanthine Phosphoribosyltransferase
    Chemical Substances Methionine (AE28F7PNPL) ; Racemethionine (73JWT2K6T3) ; Hypoxanthine Phosphoribosyltransferase (EC 2.4.2.8)
    Language English
    Publishing date 2024-02-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2036826-4
    ISSN 1476-3524 ; 1029-8428
    ISSN (online) 1476-3524
    ISSN 1029-8428
    DOI 10.1007/s12640-024-00698-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Age-Related COVID-19 Influence on Male Fertility.

    Shcherbitskaia, Anastasiia D / Komarova, Evgeniia M / Milyutina, Yulia P / Sagurova, Yanina M / Ishchuk, Mariia A / Mikhel, Anastasiia V / Ob'edkova, Ksenia V / Lesik, Elena A / Gzgzyan, Alexander M / Tapilskaya, Natalya I / Bespalova, Olesya N / Kogan, Igor Y

    International journal of molecular sciences

    2023  Volume 24, Issue 21

    Abstract: The impact of coronavirus on the reproductive health of men attracts the special attention of many researchers. While studies suggest changes in sperm parameters and the possibility of testicular inflammation, further studies are needed to elucidate any ... ...

    Abstract The impact of coronavirus on the reproductive health of men attracts the special attention of many researchers. While studies suggest changes in sperm parameters and the possibility of testicular inflammation, further studies are needed to elucidate any potential age-related changes in these findings, which is the purpose of the present study. The semen quality parameters, cytokine concentration, and markers of the pro- and antioxidant system were assessed in 60 men five to seven months after the coronavirus infection and in 77 controls (without a history of coronavirus infection). Additionally, participants were divided into two age groups: less than 35 years and 35 years or older. Notably increased round cell count in ejaculate and reduced sperm hyaluronan binding ability were observed among post-infection patients younger than 35 years. In the same group, a decline in seminal plasma zinc levels and nitrotyrosine in the cell fraction was found. In men over 35 years of age, Coronavirus Disease 2019 (COVID-19) led to increased sperm DNA fragmentation, a decrease in the total antioxidant capacity, and an elevation in the levels of interleukin-1β and interleukin-10. The concentration of interleukin-1β decreased over time following recovery in all affected patients. The data obtained suggest the potential adverse impact of the coronavirus infection on male reproductive health; however, these effects appear to be age-dependent.
    MeSH term(s) Humans ; Male ; Adult ; Semen Analysis ; Infertility, Male/etiology ; Infertility, Male/metabolism ; Semen/metabolism ; Interleukin-1beta/metabolism ; Sperm Count ; Antioxidants/metabolism ; COVID-19/metabolism ; Spermatozoa/metabolism ; Fertility ; Sperm Motility
    Chemical Substances Interleukin-1beta ; Antioxidants
    Language English
    Publishing date 2023-10-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms242115742
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Maternal Hyperhomocysteinemia Disturbs the Mechanisms of Embryonic Brain Development and Its Maturation in Early Postnatal Ontogenesis.

    Vasilev, Dmitrii S / Shcherbitskaia, Anastasiia D / Tumanova, Natalia L / Mikhel, Anastasiia V / Milyutina, Yulia P / Kovalenko, Anna A / Dubrovskaya, Nadezhda M / Inozemtseva, Daria B / Zalozniaia, Irina V / Arutjunyan, Alexander V

    Cells

    2023  Volume 12, Issue 1

    Abstract: 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 ... ...

    Abstract 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 were described. Maternal hyperhomocysteinemia was induced in female rats by per os administration of 0.15% aqueous methionine solution in the period of days 4-21 of pregnancy. Behavioral tests revealed a delay in PHHC male pups maturing. Ultrastructure of both cortical and hippocampus tissue demonstrated the features of the developmental delay. PHHC was shown to disturb both generation and radial migration of neuroblasts into the cortical plate. Elevated
    MeSH term(s) Rats ; Animals ; Female ; Pregnancy ; Male ; Rats, Wistar ; Hyperhomocysteinemia/metabolism ; Placenta/metabolism ; Brain/metabolism ; Neurogenesis
    Language English
    Publishing date 2023-01-03
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12010189
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Imbalance of Angiogenic and Growth Factors in Placenta in Maternal Hyperhomocysteinemia.

    Arutjunyan, Alexander V / Kerkeshko, Gleb O / Milyutina, Yulia P / Shcherbitskaia, Anastasiia D / Zalozniaia, Irina V / Mikhel, Anastasiia V / Inozemtseva, Daria B / Vasilev, Dmitrii S / Kovalenko, Anna A / Kogan, Igor Yu

    Biochemistry. Biokhimiia

    2023  Volume 88, Issue 2, Page(s) 262–279

    Abstract: 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 ... ...

    Abstract 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 women. However, the effect of hyperhomocysteinemia (HHcy) on the development of the placenta and, in particular, on the formation of its vascular network is at present poorly understood. The aim of this work was to study the effect of maternal HHcy on the expression of angiogenic and growth factors (VEGF-A, MMP-2, VEGF-B, BDNF, NGF), as well as their receptors (VEGFR-2, TrkB, p75NTR), in the rat placenta. The effects of HHcy were studied in the morphologically and functionally different maternal and fetal parts of the placenta on the 14th and 20th day of pregnancy. The maternal HHcy caused increase in the levels of oxidative stress and apoptosis markers accompanied by an imbalance of the studied angiogenic and growth factors in the maternal and/or fetal part of the placenta. The influence of maternal HHcy in most cases manifested in a decrease in the protein content (VEGF-A), enzymatic activity (MMP-2), gene expression (VEGFB, NGF, TRKB), and accumulation of precursor form (proBDNF) of the investigated factors. In some cases, the effects of HHcy differed depending on the placental part and stage of development. The influence of maternal HHcy on signaling pathways and processes controlled by the studied angiogenic and growth factors could lead to incomplete development of the placental vasculature and decrease in the placental transport, resulting in fetal growth restriction and impaired fetal brain development.
    MeSH term(s) Pregnancy ; Female ; Rats ; Humans ; Animals ; Placenta/metabolism ; Matrix Metalloproteinase 2/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Hyperhomocysteinemia/metabolism ; Nerve Growth Factor/metabolism ; Nerve Growth Factor/pharmacology
    Chemical Substances Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Vascular Endothelial Growth Factor A ; Nerve Growth Factor (9061-61-4)
    Language English
    Publishing date 2023-04-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297923020098
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Prenatal Hyperhomocysteinemia Induces Glial Activation and Alters Neuroinflammatory Marker Expression in Infant Rat Hippocampus.

    Shcherbitskaia, Anastasiia D / Vasilev, Dmitrii S / Milyutina, Yulia P / Tumanova, Natalia L / Mikhel, Anastasiia V / Zalozniaia, Irina V / Arutjunyan, Alexander V

    Cells

    2021  Volume 10, Issue 6

    Abstract: 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 ... ...

    Abstract 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 rats received L-methionine (0.6 g/kg b.w.) by oral administration during pregnancy. On postnatal days 5 and 20, the offspring's hippocampus was removed to perform histological and biochemical studies. After PHHC, the offspring exhibited increased brain interleukin-1β and interleukin-6 levels and glial activation, as well as reduced anti-inflammatory interleukin-10 level in the hippocampus. Additionally, the activity of acetylcholinesterase was increased in the hippocampus of the pups. Exposure to PHHC also resulted in the reduced number of neurons and disrupted neuronal ultrastructure. At the same time, no changes in the content and activity of caspase-3 were found in the hippocampus of the pups. In conclusion, our findings support the hypothesis that neuroinflammation and glial activation could be involved in altering the hippocampus cellular composition following PHHC, and these alterations could be associated with cognitive disorders later in life.
    MeSH term(s) Acetylcholinesterase/metabolism ; Animals ; Animals, Newborn ; Biomarkers/metabolism ; Brain/metabolism ; Brain/pathology ; Caspase 3/metabolism ; Cytokines/metabolism ; Female ; Hippocampus/metabolism ; Hippocampus/pathology ; Hyperhomocysteinemia/metabolism ; Hyperhomocysteinemia/pathology ; Inflammation/metabolism ; Inflammation/pathology ; Interleukin-1beta/metabolism ; Interleukin-6/metabolism ; Methionine/metabolism ; Neuroglia/metabolism ; Neuroglia/pathology ; Neurons/metabolism ; Neurons/pathology ; Pregnancy ; Prenatal Exposure Delayed Effects/metabolism ; Prenatal Exposure Delayed Effects/pathology ; Rats ; Rats, Wistar
    Chemical Substances Biomarkers ; Cytokines ; Interleukin-1beta ; Interleukin-6 ; Methionine (AE28F7PNPL) ; Acetylcholinesterase (EC 3.1.1.7) ; Caspase 3 (EC 3.4.22.-)
    Language English
    Publishing date 2021-06-18
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10061536
    Database MEDical Literature Analysis and Retrieval System OnLINE

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