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Alexander V. Sirotkin

Bio: Alexander V. Sirotkin is an academic researcher from University of Constantine the Philosopher. The author has contributed to research in topics: Ovary & Apoptosis. The author has an hindex of 26, co-authored 193 publications receiving 2525 citations.
Topics: Ovary, Apoptosis, Growth factor, Hormone, Medicine


Papers
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Journal ArticleDOI
TL;DR: It is demonstrated that miRNAs can control reproductive functions resulting in enhanced or inhibited release of ovarian progestagen, androgen and estrogen, the first demonstration that miRNA‐mediated effects could be potentially used for regulation of reproductive processes.
Abstract: The aim of our studies was to identify miRNAs affecting the release of the major ovarian steroid hormones progestagen, androgen and estrogen by human ovarian cells. The effect of transfection of cultured primary ovarian granulosa cells with 80 different gene constructs encoding human pre-miRNAs on release of progesterone, testosterone and estradiol was evaluated by enzyme immunoassay. In addition, effect of two selected antisense constructs blocking corresponding miRNA on progesterone release was tested. Efficiency of transfection (incorporation transfection reagent) and silencing of marker substances (GAPDH mRNA, GAPDH and CREB-1) were validated by fluorescent microscopy, real-time reverse transcription-PCR analysis and immunocytochemical analysis. Thirty-six out of 80 tested miRNA constructs resulted in inhibition of progesterone release in granulosa cells, and 10 miRNAs promoted progesterone release. Transfected of cells with antisense constructs to two selected miRNAs blocking progesterone release induced increase in progesterone output. Fifty-seven miRNAs tested inhibited testosterone release, and only one miRNA enhanced testosterone output. Fifty-one miRNAs suppressed estradiol release, while none of the miRNAs tested stimulated it. This is the first demonstration that miRNAs can control reproductive functions resulting in enhanced or inhibited release of ovarian progestagen, androgen and estrogen. We hypothesize that such miRNA-mediated effects could be potentially used for regulation of reproductive processes, including fertility, and for treatment of reproductive and other steroid-dependent disorders.

191 citations

Journal ArticleDOI
TL;DR: This is the first direct demonstration of the involvement of miRNAs in controlling both proliferation and apoptosis by ovarian granulose cells, as well as the identification of mi RNAs promoting and suppressing these processes utilizing a genome‐wide miRNA screen.
Abstract: Previous studies have shown that microRNAs (miRNAs) can control steroidogenesis in cultured granulosa cells. In this study we wanted to determine if miRNAs can also affect proliferation and apoptosis in human ovarian cells. The effect of transfection of cultured primary ovarian granulosa cells with 80 different constructs encoding human pre-miRNAs on the expression of the proliferation marker, PCNA, and the apoptosis marker, Bax was evaluated by immunocytochemistry. Eleven out of 80 tested miRNA constructs resulted in stimulation, and 53 miRNAs inhibited expression of PCNA. Furthermore, 11 of the 80 miRNAs tested promoted accumulation of Bax, while 46 miRNAs caused a reduction in Bax in human ovarian cells. In addition, two selected antisense constructs that block the corresponding miRNAs mir-15a and mir-188 were evaluated for their effects on expression of PCNA. An antisense construct inhibiting mir-15a (which precursor suppressed PCNA) increased PCNA, whereas an antisense construct for mir-188 (which precursor did not change PCNA) did not affect PCNA expression. Verification of effects of selected pre-mir-10a, mir-105, and mir-182 by using other markers of proliferation (cyclin B1) and apoptosis (TdT and caspase 3) confirmed specificity of miRNAs effects on these processes. This is the first direct demonstration of the involvement of miRNAs in controlling both proliferation and apoptosis by ovarian granulose cells, as well as the identification of miRNAs promoting and suppressing these processes utilizing a genome-wide miRNA screen.

175 citations

Journal ArticleDOI
TL;DR: The aim of this review was to compile the evidence concerning the association between phthalates and reproductive diseases, phthalate-induced reproductive disorders, and their possible endocrine and intracellular mechanisms.
Abstract: The production of plastic products, which requires phthalate plasticizers, has resulted in the problems for human health, especially that of reproductive health. Phthalate exposure can induce reproductive disorders at various regulatory levels. The aim of this review was to compile the evidence concerning the association between phthalates and reproductive diseases, phthalates-induced reproductive disorders, and their possible endocrine and intracellular mechanisms. Phthalates may induce alterations in puberty, the development of testicular dysgenesis syndrome, cancer, and fertility disorders in both males and females. At the hormonal level, phthalates can modify the release of hypothalamic, pituitary, and peripheral hormones. At the intracellular level, phthalates can interfere with nuclear receptors, membrane receptors, intracellular signaling pathways, and modulate gene expression associated with reproduction. To understand and to treat the adverse effects of phthalates on human health, it is essential to expand the current knowledge concerning their mechanism of action in the organism.

86 citations

Journal ArticleDOI
TL;DR: The results are the first demonstration that obestatin directly controls porcine ovarian cell functions: it can stimulate proliferation, accumulation of rPCNA, cyclin B1 and MAPK, apoptosis, and the secretion of progesterone.

61 citations

Journal ArticleDOI
TL;DR: It is demonstrated that IGF-I is a potent stimulator of ovarian secretion, proliferation and embryogenesis in rabbit and its effects are mediated by cAMP/PKA- and, probably by, MAPK-dependent intracellular mechanisms.

58 citations


Cited by
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Journal ArticleDOI
TL;DR: Extant evidence favors roles for ghrelin in both short-term meal initiation and long-term energy homeostasis, making it an attractive target for drugs to treat obesity and/or wasting disorders.

603 citations

Journal Article

392 citations

Journal ArticleDOI
TL;DR: It is proposed that 17 beta-estradiol relaxes coronary arteries by opening BKCa channels via cGMP-dependent phosphorylation, which could account for the hypotensive effect of estrogens and help explain, at least in part, why postmenopausal estrogen therapy lowers the risk of cardiovascular disease.
Abstract: Women rarely suffer cardiovascular dysfunction before menopause, but by the age of 65 a woman becomes as vulnerable to cardiovascular mortality as a man. It has been proposed that estrogens protect against cardiovascular disease; however, the physiological basis of estrogen protection is unknown. In the present study the mechanism of estrogen-induced relaxation of coronary arteries was investigated at the tissue, cellular, and molecular levels. Tissue studies demonstrated that 17β-estradiol relaxes porcine coronary arteries by an endothelium-independent mechanism involving K+ efflux, and subsequent studies employing the patch-clamp technique confirmed that estrogen stimulates K+ channel gating in coronary smooth muscle. Perforated-patch recordings from metabolically intact coronary myocytes revealed that 17β-estradiol more than doubles steady state outward currents in these cells at positive voltages. Studies of on-cell patches demonstrated a potent stimulatory effect of 17β-estradiol on the gati...

362 citations

Book
26 Feb 1998
TL;DR: In this article, the authors discuss the effects of chemicals in the environment on humans and their effect on humans' health, including the effects on their health on animals and on the environment.
Abstract: Preface Contents Special Topics 1. Environmental Toxicology and Chemistry 1.1 Poisons 1.2 Environmental Toxicology 1.3 Environmental Chemistry 1.4 Toxicity 1.5 Intoxication 1.5.1 Humans 1.5.2 Domestic Animals 1.5.3 Wildlife 1.5.4 Plants and Microorganisms 1.5.5 Ecosystems 1.6 Hazard and Risk 1.7 Major Toxic Hazards 1.8 Perspecive 1.9 References Special Topic 1: Ecotoxicology 2. Chemicals in the Environment 2.1 Chemicals in the Environment 2.2 Detection and Measurement 2.3 The Atmosphere 2.3.1 The Natural Atmosphere 2.3.2 Polluted Atmospheres 2.3.3 Indoor Air 2.4 Water 2.4.1 Natural Waters 2.4.2 Polluted Waters 2.5 Soils 2.5.1 Soil Composition 2.5.2 Toxic Waste 2.5.3 Pesticides 2.6 Biota 2.6.1 Toxic Organisms 2.6.2 Food 2.7 Chemicals in Everyday Life 2.8 References Special Topic 2: Pesticide Residues 3. Environmental Chemodynamics 3.1 Environmental Chemodynamics 3.2 Dissolution 3.3 Solvent Partitioning 3.4 Volitilization 3.5 Adsorption 3.6 Significance 3.7 References Special Topic 3: The Great Escape 4. Environmental Transport 4.1 Dissipation of Chemicals 4.2 Transport In and From Surface Water 4.2.1 Transport in solution 4.2.2 Transport between water and air 4.2.3 Transport on particles 4.3 Transport in Soil and Groundwater 4.3.1 Transport through soil 4.3.2 Transport in groundwater 4.4 Atmospheric Transport 4.4.1 Volatilization 4.4.2 Advection 4.4.3 Deposition 4.5 Commerical Conveyance 4.6 Global Transport 4.7 References Special Topic 4: Wind, Water, and Waves 5. Abiotic Transformations 5.1 Transformations 5.2 Photochemistry 5.2.1 Radiant energy 5.2.2 Photochemical recations 5.2.3 Solar energy 5.3 Oxidation 5.3.1 Radical oxidations 5.3.2 Atmospheric oxidants 5.3.3 Photochemical smog 5.3.4 Oxidations in water 5.3.5 Oxidations in soil 5.4 Reduction 5.4.1 Redox potentials 5.4.2 Reductions in soil 5.4.3 Reductions in water 5.5 Hydrolysis 5.5.1 Water 5.5.2 Hydrolysis in water 5.5.3 Hydrolysis in soil 5.6 Some Other Reactions 5.6.1 Alkylation 5.6.2 Beta-elimination 5.6.3 Chlorination 5.7 Summary of Abiotic Reactions 5.8 References Special Topic 5: Free Radicals and the Ozone Layer 6. Biotransformations 6.1 Biotransformations 6.2 Transformations by Microorganisms 6.2.1 Microorganisms 6.2.2 Oxidation 6.2.3 Cytochrome P450 6.2.4 Reduction 6.2.5 Hydrolysis 6.2.6 Other transformations 6.3 Transformations in Animals and Higher Plants 6.3.1 Primary (Phase I) metabolism 6.3.2 Secondary (Phase II) metabolism 6.4 Comparative Metabolism 6.5 References Special Topic 6: Anatomy of an Oil Spill 7. Intoxication 7.1 The Intoxication Process 7.2 Absorption and Disposition 7.2.1 Absorption 7.2.2 Disposition 7.2.3 Elimination 7.3 Factors Governing Intoxication 7.3.1 Metabolism (Biodegradation) 7.3.2 Bioavailability 7.3.3 Individual and species differences 7.3.4 Other factors 7.4 Toxic Effects 7.4.1 "Poisoning" 7.4.2 The nervous system 7.4.3 The skin 7.4.4 The respiratory system 7.4.5 Blood and internal organs 7.4.6 The reproductive system 7.4.7 Genes 7.5 References Special Topic 7: Adaption 8. Quantitative Toxicology 8.1 Dose-Response Relations 8.2 Factors Affecting Quantitative Responses 8.3 Toxicokinetics 8.4 Toxicity Measurements and Endpoints 8.4.1 Measurements 8.4.2 Acute toxicity 8.4.3 Life-cycle tests 8.4.4 Other bioassays 8.4.5 Mutagenicity tests 8.4.6 Phytotoxicity 8.4.7 Toxiciy tests for pesticide registration 8.4.8 Ethics and alternatives 8.5 Data from Humans 8.5.1 Toxicity tests 8.5.2 Mortality statistics 8.5.3 Exposure data 8.5.4 Epidemiology 8.6 References Special Topic 8: Epidemiology 9. Intoxication Mechanisms 9.1 The Biochemical Lesion 9.2 Receptors and Targets 9.3 Mechanisms of General Toxicity 9.4 Animal-specific Mechanisms 9.4.1 Nervous system 9.4.2 Liver 9.4.3 Intermediary metabolism 9.5 Plant-specific Mechanisms 9.5.1 Photosynthesis 9.5.2 Amino Acid biosynthesis 9.6 Microbe-specific Mechanisms 9.6.1 Cell wall synthesis 9.6.2 Sulfhydryl groups 9.7 Perspective 9.8 References Special Topic 9: Chemical Carcinogens 10. Exposure and Risk 10.1 Hazard and Risk 10.2 Exposure 10.3 Risk Assessments 10.3.1 Occupational exposure 10.3.2 Exposure at home 10.3.3 Risk characterization 10.4 Ecological Risk 10.4.1 Toxicity data 10.4.2 Scaling 10.4.3 Ecosystem risk 10.5 Risk management 10.5.1 Regulations 10.5.2 Risk communication 10.6 References Special Topic 10: PBPK Models 11. Inorganic Toxicants 11.1 Inorganic Toxicants 11.2 Some Basic Chemistry 11.3 Nonmetallic Elements 11.4 The Metalloids 11.4.1 Metalloids 11.4.2 Arsenic 11.4.3 Selenium 11.4.4 Tin 11.5 Heavy Elements 11.5.1 The heavy metals 11.5.2 Mercury 11.5.3 Lead 11.5.4 Thallium and bismuth 11.6 Transition Elements 11.6.1 Transition metals 11.6.2 Copper 11.6 3 Other transition elements 11.7 Radioactive elements 11.8 Other Toxic Elements 11.9 References Special Topic 11: Methylation of Metals and Metalloids 12. Biotoxins 12.1 Biotoxins 12.2 Alkaloids 12.3 Toxic Glycosides 12.4 Plant Phenolics 12.5 Amino Acids, Peptides, and Proteins 12.6 Lactone Mycotoxins 12.7 Perspective 12.8 References Special Topic 12: Allelochemicals 13. Industrial Chemicals 13.1 Industrial Chemicals 13.1.1 Minerals 13.1.2 Petroleum 13.2 Petrochemicals 13.2.1 Sources 13.2.2 Major petrochemicals 13.3 Toxic Byproducts and Conversion Products 13.3.1 Origin 13.3.2 Polycyclic aromatic hydrocarbons (PAH) 13.3.3 Hex waste 13.3.4 Chlorinated dioxins 13.4 References Special Topic 13: Why Chlorinate? 14. Refractory Pollutants 14.1 Refractory Chemicals 14.2 DDT and DDE 14.2.1 Background 14.2.2 Toxicity 14.2.3 Transport and transformation 14.2.4 DDE 14.3 Chlorinated Alicyclics 14.3.1 Benzene hexachloride (BHC) 14.3.2 Cyclodienes 14.3.3 Other organochlorine insecticides 14.4 Chlorinated Dioxins 14.5 Polychlorinated Biphenyls 14.6 Phthalate Esters 14.7 Perspective 14.8 References Special Topic 14: Environmental Persistence 15. Reactive Pollutants 15.1 Reactivity 15.2 Alkyl Halides 15.3 Chlorophenols 15.4 Divalent Sulfur Compounds 15.5 Dithioarbamates 15.6 Nitroarenes 15.7 Amines and Their Derivatives 15.8 Esters 15.9 Carbon Monoxide and Cyanides 15.10 Perspective 15.11 References Special Topic 15: Hazardous Waste 16. Predicting Environmental Fate and Toxicity 16.1 Quantitative Prediction 16.2 Predicting Environmental Transport 16.2.1 Linear free energy relations 16.2.2 Octanol-water partition coefficients 16.2.3 Bioconcentration factors 16.2.4 Aqueous solubility 16.2.5 Volatilization 16.2.6 Soil sorption coefficients 16.3 Predicting Environmental Transformations 16.3.1 Reactions and products 16.3.2 Equilibria and rates 16.4 Modelling Environmental Fate 16.5 Quantitative Structure-activity Relations (QSAR) 16.6 Microcosms (Model Ecosystems) 16.7 References Special Topic 16: QSAR and Toxicity GLOSSARY INDEX

327 citations