astmedАстраханский медицинский журналAstrakhan medical journal1992-6499ФГБОУ ВО Астраханский ГМУ Минздрава России10.48612/agmu/2022.17.1.14.22astmed-147Research ArticleНАУЧНЫЕ ОБЗОРЫSCIENTIFIC REVIEWSРОЛЬ ФАКТОРА ДИФФЕРЕНЦИРОВКИ РОСТА-15 (GDF-15) В РЕГУЛЯЦИИ И РАЗВИТИИ ОСЛОЖНЕНИЙ БЕРЕМЕННОСТИSCIENTIFIC REVIEWS Review article THE ROLE OF GROWTH DIFFERENTIATION FACTOR-15 (GDF-15) IN THE REGULATION AND THE DEVELOPMENT OF PREGNANCY COMPLICATIONSТишковаО. Г.TishkovaO. G.tishkov2003@mail.ruДикареваЛ. В.DikarevaL. V.dikarevalv@mail.ruШваревЕ. Г.ShvarevE. G.geshvarev09@mail.ruУхановаЮ. Ю.UkhanovaY. Yu.yulli20@mail.ruАстраханский государственный медицинский университетРоссияAstrakhan State Medical UniversityRussian Federation2022270220231711422Copyright © Тишкова О.Г., Дикарева Л.В., Шварев Е.Г., Уханова Ю.Ю., 20232023Тишкова О.Г., Дикарева Л.В., Шварев Е.Г., Уханова Ю.Ю.Tishkova O.G., Dikareva L.V., Shvarev E.G., Ukhanova Y.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.astmedj.ru/jour/article/view/147

Изучено клиническое значение одного из малоизученных цитокинов - фактора дифференцировки роста -15 (GDF-15) в процессе регуляции клеточных и молекулярных процессов во время беременности. Современные исследования механизмов активации клеточных путей GDF-15 позволяют рассматривать этот белок в качестве одного из важных регуляторов метаболических процессов и иммунологической толерантности. Неоднозначные результаты исследований GDF-15 при различной патологии свидетельствуют о его сложной регуляции и многофункциональности. Высокие уровни циркуляции этого цитокина в сыворотке крови и в плаценте указывают на важное значение этого белка в реализации иммунного ответа при беременности, которое еще предстоит объяснить.

The clinical significance of one of the little-studied cytokines - growth differentiation factor -15 (GDF-15) in the process of regulation of cellular and molecular processes during pregnancy was studied. Current studies of the mechanisms of activation of cellular pathways GDF-15 allow us to consider this protein as one of the important regulators of metabolic processes and immunological tolerance. The mixed results of GDF-15 studies with various pathologies indicate its complex regulation and multifunctionality. High levels of circulation of this cytokine in serum and placenta indicate the importance of this protein in the realization of the immune response in pregnancy, which has yet to be explained.

фактор дифференцировки роста (GDF-15)беременностьбелокцитокиныgrowth differentiation factor (GDF-15)pregnancyproteinscytokinesReferencesAlbonici L., Benvenuto M., Focaccetti C., Cifaldi L., Miele M., Limana F., Manzari V., Bei R. PlGF Immunological Impact during Pregnancy // International Journal of Molecular Sciences. 2020. Vol. 21, no. 22. P. 8714-8740. doi: 10.3390/ijms21228714.Albonici L., Benvenuto M., Focaccetti C., Cifaldi L., Miele M., Limana F., Manzari V., Bei R. PlGF Immunological Impact during Pregnancy // International Journal of Molecular Sciences. 2020. Vol. 21, no. 22. P. 8714-8740. doi: 10.3390/ijms21228714.Маснавиева Л. Б. Интегральные лейкоцитарные индексы и уровни цитокинов у городских подростков с различным содержанием специфических аутоантител // Астраханский медицинский журнал. 2017. Т. 12, № 1. С. 50-55.Маснавиева Л. Б. Интегральные лейкоцитарные индексы и уровни цитокинов у городских подростков с различным содержанием специфических аутоантител // Астраханский медицинский журнал. 2017. Т. 12, № 1. С. 50-55.Ander S. E., Diamond M. S., Coyne C. B. Immune responses at the maternal-fetal interface// Science Immunology. 2019. Vol. 4, no. 31. P. 6114-6124. doi: 10.1126/sciimmunol.aat6114.Ander S. E., Diamond M. S., Coyne C. B. Immune responses at the maternal-fetal interface// Science Immunology. 2019. Vol. 4, no. 31. P. 6114-6124. doi: 10.1126/sciimmunol.aat6114.Bootcov M. R., Bauskin A. R., Valenzuela S. M., Moore A. G., Bansal M., He X. Y., Zhang H. P., Donnellan M., Mahler S., Pryor K., Walsh B. J., Nicholson R. C., Fairlie W. D., Por S. B., Robbins J. M., Breit S. N. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily // Proceedings of the National Academy of Sciences of the USA. 1997. Vol. 94, no. 21. P. 11514-11519. doi: 10.1073/pnas.94.21.11514Bootcov M. R., Bauskin A. R., Valenzuela S. M., Moore A. G., Bansal M., He X. Y., Zhang H. P., Donnellan M., Mahler S., Pryor K., Walsh B. J., Nicholson R. C., Fairlie W. D., Por S. B., Robbins J. M., Breit S. N. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily // Proceedings of the National Academy of Sciences of the USA. 1997. Vol. 94, no. 21. P. 11514-11519. doi: 10.1073/pnas.94.21.11514Emmerson P., Duffin K., Chintharlapalli S., Wu X. GDF15 and Growth Control // Frontiersin Physiology. 2018. Vol. 9. P. 1712-1719. doi: 10.3389/fphys.2018.01712.Emmerson P., Duffin K., Chintharlapalli S., Wu X. GDF15 and Growth Control // Frontiersin Physiology. 2018. Vol. 9. P. 1712-1719. doi: 10.3389/fphys.2018.01712.Ahmed D. S., Isnard S., Lin J., Routy B., Routy J. P. GDF15/GFRAL Pathway as a Metabolic Signature for Cachexia in Patients with Cancer // Journal of Cancer. 2021. Vol. 12, № 4. P. 1125-1132. doi: 10.7150/jca.50376.Ahmed D. S., Isnard S., Lin J., Routy B., Routy J. P. GDF15/GFRAL Pathway as a Metabolic Signature for Cachexia in Patients with Cancer // Journal of Cancer. 2021. Vol. 12, № 4. P. 1125-1132. doi: 10.7150/jca.50376.Moore A. G., Brown D. A., Fairlie W. D., Bauskin A. R., Brown P. K., Munier M. L., Russell P. K., Salamonses L. A., Wallace E. M., Breit S. N. The transforming growth factors - ss superfamily cytokine macrophage inhibitory cytokine-1 is present in high concentrations in the serum of pregnant women // The Journal Clinical Endocrinology and Metabolism. 2000. Vol. 85, no. 12. P. 4781-4788. doi:org/10.1210/jcem.85.12.7007.Moore A. G., Brown D. A., Fairlie W. D., Bauskin A. R., Brown P. K., Munier M. L., Russell P. K., Salamonses L. A., Wallace E. M., Breit S. N. The transforming growth factors - ss superfamily cytokine macrophage inhibitory cytokine-1 is present in high concentrations in the serum of pregnant women // The Journal Clinical Endocrinology and Metabolism. 2000. Vol. 85, no. 12. P. 4781-4788. doi:org/10.1210/jcem.85.12.7007.Lawton L. N., Bonaldo M. F., Jelenc P. C., Qiu L., Baumes S. A, Marcelino R. A., de Jesus G. M., Wellington S., Knowles J. A., Warburton D., Brown S., Soares M. B. Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta // Gene. 1997. Vol. 203, no. 1. P. 17-26. doi: 10.1016/s0378-1119(97)00485-x.Lawton L. N., Bonaldo M. F., Jelenc P. C., Qiu L., Baumes S. A, Marcelino R. A., de Jesus G. M., Wellington S., Knowles J. A., Warburton D., Brown S., Soares M. B. Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta // Gene. 1997. Vol. 203, no. 1. P. 17-26. doi: 10.1016/s0378-1119(97)00485-x.Böttner M., Suter-Crazzolara C., Schober A., Unsicker K. Expression of a novel member of the TGF-beta superfamily, growth/differentiation factor-15/macrophage-inhibiting cytokine-1 (GDF-15/MIC-1) in adult rat tissues // Cell Tissue Research. 1999. Vol. 297, no. 1. P. 103-110. doi: 10.1007/s004410051337.Böttner M., Suter-Crazzolara C., Schober A., Unsicker K. Expression of a novel member of the TGF-beta superfamily, growth/differentiation factor-15/macrophage-inhibiting cytokine-1 (GDF-15/MIC-1) in adult rat tissues // Cell Tissue Research. 1999. Vol. 297, no. 1. P. 103-110. doi: 10.1007/s004410051337.Hromas R., Hufford M., Sutton J., Xu D., Li Y., Lu L. PLAB, a novel placental bone morphogenetic protein // Biochimica et Biophysica Acta. 1997. Vol. 1354, no. 1. P. 40-44. doi: 10.1016/s0167-4781(97)00122-x.Hromas R., Hufford M., Sutton J., Xu D., Li Y., Lu L. PLAB, a novel placental bone morphogenetic protein // Biochimica et Biophysica Acta. 1997. Vol. 1354, no. 1. P. 40-44. doi: 10.1016/s0167-4781(97)00122-x.Herpin A., Lelong C., Favrel P. Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans // Developmental and Comparative Immunology. 2004. Vol. 28, no. 5. P. 461-485. doi: 10.1016/j.dci.2003.09.007.Herpin A., Lelong C., Favrel P. Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans // Developmental and Comparative Immunology. 2004. Vol. 28, no. 5. P. 461-485. doi: 10.1016/j.dci.2003.09.007.Wischhusen J., Melero I., Fridman W. H. Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint // Frontiers Immunology. 2020. Vol. 11. P. 951-970. doi: 10.3389/fimmu.2020.00951.Wischhusen J., Melero I., Fridman W. H. Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint // Frontiers Immunology. 2020. Vol. 11. P. 951-970. doi: 10.3389/fimmu.2020.00951.Bauskin A. R., Jiang L., Luo X. W., Wu L., Brown D. A., Breit S. N. The TGF-beta superfamily cytokine MIC-1/GDF15: secretory mechanisms facilitate creation of latent stromal stores // Journal of Interferon and Cytokine Research. 2010. Vol. 30. P. 389-397. doi: 10.1089/jir.2009.0052.Bauskin A. R., Jiang L., Luo X. W., Wu L., Brown D. A., Breit S. N. The TGF-beta superfamily cytokine MIC-1/GDF15: secretory mechanisms facilitate creation of latent stromal stores // Journal of Interferon and Cytokine Research. 2010. Vol. 30. P. 389-397. doi: 10.1089/jir.2009.0052.Brown D. A., Bauskin A. R., Fairlie W. D., Smith M. D., Liu T., Xu N., Breit S. N. Antibody-based approach to high-volume genotyping for MIC-1 polymorphism // Biotechniques. 2002. Vol. 33, no. 1. P.118-120. doi: 10.2144/02331rr03.Brown D. A., Bauskin A. R., Fairlie W. D., Smith M. D., Liu T., Xu N., Breit S. N. Antibody-based approach to high-volume genotyping for MIC-1 polymorphism // Biotechniques. 2002. Vol. 33, no. 1. P.118-120. doi: 10.2144/02331rr03.Xiong Y., Walker K., Min X., Hale C., Tran T., Komorowski R., Yang J., Davda J., Nuanmanee N., Kemp D., Wang X., Liu H., Miller S., Lee K. J., Wang Z., Veniant M. M. Long-acting MIC-1/GDF15 molecules to treat obesity: evidence from mice to monkeys // Science Translational Medicine. 2017. Vol. 9, no. 412. P. 8732-8740. doi: 10.1126/scitranslmed.aan8732.Xiong Y., Walker K., Min X., Hale C., Tran T., Komorowski R., Yang J., Davda J., Nuanmanee N., Kemp D., Wang X., Liu H., Miller S., Lee K. J., Wang Z., Veniant M. M. Long-acting MIC-1/GDF15 molecules to treat obesity: evidence from mice to monkeys // Science Translational Medicine. 2017. Vol. 9, no. 412. P. 8732-8740. doi: 10.1126/scitranslmed.aan8732.Tsai V. W. W., Husaini Y., Sainsbury A., Brown D. A., Breit S. N. The MIC-1/GDF15-GFRAL pathway in energy homeostasis: implications for obesity, cachexia, and other associated diseases // Cell Metabolism. 2018. Vol. 28. P. 353-368. doi: 10.1016/j.cmet.2018.07.018Tsai V. W. W., Husaini Y., Sainsbury A., Brown D. A., Breit S. N. The MIC-1/GDF15-GFRAL pathway in energy homeostasis: implications for obesity, cachexia, and other associated diseases // Cell Metabolism. 2018. Vol. 28. P. 353-368. doi: 10.1016/j.cmet.2018.07.018Bermúdez B., López S., Pacheco Y. M., Villar J., Muriana F. J., Hoheisel J. D., Bauer A., Abia R., Influence of postprandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coronary artery // Cardiovascular Research. 2008. Vol. 79, no. 2. P. 294-303. doi: org/10.1093/cvr/cvn082.Bermúdez B., López S., Pacheco Y. M., Villar J., Muriana F. J., Hoheisel J. D., Bauer A., Abia R., Influence of postprandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coronary artery // Cardiovascular Research. 2008. Vol. 79, no. 2. P. 294-303. doi: org/10.1093/cvr/cvn082.Ding Q., Mracek T., Gonzalez-Muniesa P., Kos K., Wilding J., Trayhurn P., Bing C., Identification of Macrophage Inhibitory Cytokine-1 in Adipose Tissue and Its Secretion as an Adipokine by Human Adipocytes // Endocrinology. 2009. Vol. 150, no. 4. P. 1688-1696. doi.org/10.1210/en.200-0952.Ding Q., Mracek T., Gonzalez-Muniesa P., Kos K., Wilding J., Trayhurn P., Bing C., Identification of Macrophage Inhibitory Cytokine-1 in Adipose Tissue and Its Secretion as an Adipokine by Human Adipocytes // Endocrinology. 2009. Vol. 150, no. 4. P. 1688-1696. doi.org/10.1210/en.200-0952.Ferrari N., Pfeffer U., Dell'Eva R., Ambrosini C., Noonan D., Albini A. The transforming growth factor-β family members bone morphogenetic protein-2 and macrophage inhibitory cytokine-1 as mediators of the antiangiogenic activity of N-(4-hydroxyphenyl) retinamide // Clinical Cancer Research. 2005. Vol. 11, no. 12. P. 4610-4619. doi:10.1158/1078-0432.CCR-04-2210.Ferrari N., Pfeffer U., Dell'Eva R., Ambrosini C., Noonan D., Albini A. The transforming growth factor-β family members bone morphogenetic protein-2 and macrophage inhibitory cytokine-1 as mediators of the antiangiogenic activity of N-(4-hydroxyphenyl) retinamide // Clinical Cancer Research. 2005. Vol. 11, no. 12. P. 4610-4619. doi:10.1158/1078-0432.CCR-04-2210.Uhlen M., Fagerberg L., Hallstrom B. M., Lindskog C., Oksvold P., Mardinoglu A., Sivertsson A., Kampf C., Sjostedt E., Asplund A., Olsson I., Edlund K., Lundberg E., Navani S., Szigyarto C. A-K., Odeberg J., Djureinovic D., Takanen J. O., Hober S., Alm T., Edqvist P-H., Berling H., Tegel H., Mulder J., Rockberg J., Nilsson P., Schwenk J. M., Hamsten M., Feilitzen K., Forsberg M., Persson L., Johansson F., Zwahlen M., Heijne G., Nielsen J., Ponten F. Proteomics. Tissue-based map of the human proteome // Science. 2015. Vol. 347. P. 6220-6230 doi: 10.1126/science.1260419.Uhlen M., Fagerberg L., Hallstrom B. M., Lindskog C., Oksvold P., Mardinoglu A., Sivertsson A., Kampf C., Sjostedt E., Asplund A., Olsson I., Edlund K., Lundberg E., Navani S., Szigyarto C. A-K., Odeberg J., Djureinovic D., Takanen J. O., Hober S., Alm T., Edqvist P-H., Berling H., Tegel H., Mulder J., Rockberg J., Nilsson P., Schwenk J. M., Hamsten M., Feilitzen K., Forsberg M., Persson L., Johansson F., Zwahlen M., Heijne G., Nielsen J., Ponten F. Proteomics. Tissue-based map of the human proteome // Science. 2015. Vol. 347. P. 6220-6230 doi: 10.1126/science.1260419.Ramberg H., Eide T., Krobert K. A., Levy F. O., Dizeyi N., Bjartell A. S., Abrahamsson P. A., Taskén K. A. Hormonal regulation of beta2-adrenergic receptor level in prostate cancer // The Prostate. 2008. Vol. 68, no. 10. P. 1133-1142. doi: 10.1002/pros.20778. PMID: 18454446.Ramberg H., Eide T., Krobert K. A., Levy F. O., Dizeyi N., Bjartell A. S., Abrahamsson P. A., Taskén K. A. Hormonal regulation of beta2-adrenergic receptor level in prostate cancer // The Prostate. 2008. Vol. 68, no. 10. P. 1133-1142. doi: 10.1002/pros.20778. PMID: 18454446.Cardoso A. L., Fernandes A., Aguilar-Pimentel J. A., de Angelis M. H., Guedes J. R., Brito M. A., Ortolano S., Pani G., Athanasopoulou S., Gonos E. S., Schosserer M., Grillari J., Peterson P., Tuna B. G., Dogan S., Meyer A., van Os R., Trendelenburg A. U. Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases //Ageing Research Reviews. 2018. Vol. 47. P. 214-277. doi: 10.1016/j.arr.2018.07.004.Cardoso A. L., Fernandes A., Aguilar-Pimentel J. A., de Angelis M. H., Guedes J. R., Brito M. A., Ortolano S., Pani G., Athanasopoulou S., Gonos E. S., Schosserer M., Grillari J., Peterson P., Tuna B. G., Dogan S., Meyer A., van Os R., Trendelenburg A. U. Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases //Ageing Research Reviews. 2018. Vol. 47. P. 214-277. doi: 10.1016/j.arr.2018.07.004.Kim K. H., Lee M. S. GDF15 as a central mediator for integrated stress response and a promising therapeutic molecule for metabolic disorders and NASH // Biochimica Biophysic Acta (BBA) General Subject. 2021. Vol. 1865, no. 3. Р. 70-84. doi: 10.1016/j.bbagen.2020.129834. Epub 2020 Dec 25. PMID: 33358864.Kim K. H., Lee M. S. GDF15 as a central mediator for integrated stress response and a promising therapeutic molecule for metabolic disorders and NASH // Biochimica Biophysic Acta (BBA) General Subject. 2021. Vol. 1865, no. 3. Р. 70-84. doi: 10.1016/j.bbagen.2020.129834. Epub 2020 Dec 25. PMID: 33358864.Fujita Y., Ito M., Ohsawa I. Mitochondrial stress and GDF15 in the pathophysiology of sepsis // Archives of Biochemistry Biophysics. 2020. Vol. 696. P. 113-126. doi: 10.1016/j.abb.2020.108668.Fujita Y., Ito M., Ohsawa I. Mitochondrial stress and GDF15 in the pathophysiology of sepsis // Archives of Biochemistry Biophysics. 2020. Vol. 696. P. 113-126. doi: 10.1016/j.abb.2020.108668.Assadi A., Zahabi A., Hart R. A. GDF15, an update of the physiological and pathological roles it plays: a review // Pflugers Archiv - European Journal of Physiology. 2020. Vol. 472, no. 11. P. 1535-1546. doi: 10.1007/s00424-020-02459-1.Assadi A., Zahabi A., Hart R. A. GDF15, an update of the physiological and pathological roles it plays: a review // Pflugers Archiv - European Journal of Physiology. 2020. Vol. 472, no. 11. P. 1535-1546. doi: 10.1007/s00424-020-02459-1.Adela R., Banerjee S. K. GDF-15 as a target and biomarker for diabetes and cardiovascular diseases: a translational prospective // Journal Diabetes Research. 2015. Vol. 2015. P. 1-14. doi: 10.1155/2015/490842.Adela R., Banerjee S. K. GDF-15 as a target and biomarker for diabetes and cardiovascular diseases: a translational prospective // Journal Diabetes Research. 2015. Vol. 2015. P. 1-14. doi: 10.1155/2015/490842.Michelsen T. M., Henriksen T., Reinhold D., Powell T. L., Jansson T. The human placental proteome secreted into the maternal and fetal circulations in normal pregnancy based on 4-vessel sampling// FASEB Journal. 2019. Vol. 33, no. 2. P. 2944-2956. doi: 10.1096/fj.201801193R.Michelsen T. M., Henriksen T., Reinhold D., Powell T. L., Jansson T. The human placental proteome secreted into the maternal and fetal circulations in normal pregnancy based on 4-vessel sampling// FASEB Journal. 2019. Vol. 33, no. 2. P. 2944-2956. doi: 10.1096/fj.201801193R.Brown D. A., Breit S. N., Buring J., Fairlie W. D., Bauskin A. R., Liu T., Ridker P. M. Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women: a nested case - control study // The Lancet. 2002. Vol. 359. P. 2159-2163. doi: 10.1016/S0140-6736(02)09093-1.Brown D. A., Breit S. N., Buring J., Fairlie W. D., Bauskin A. R., Liu T., Ridker P. M. Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women: a nested case - control study // The Lancet. 2002. Vol. 359. P. 2159-2163. doi: 10.1016/S0140-6736(02)09093-1.Hagström E., Held C., Stewart R. A. H., Aylward P. E., Budaj A., Cannon C. P., Koenig W., Krug-Gourley S., Mohler E. R., Steg P. G., Tarka E., Ostlund O., White H., Siegbahn A., Wallentin L. Growth differentiation factor 15 predicts all - cause morbidity and mortality in stable coronary heart disease // Clinical Chemistry. 2017. Vol. 63, no. 1. P. 325-333. doi: 10.1373/clinchem.2016.260570.Hagström E., Held C., Stewart R. A. H., Aylward P. E., Budaj A., Cannon C. P., Koenig W., Krug-Gourley S., Mohler E. R., Steg P. G., Tarka E., Ostlund O., White H., Siegbahn A., Wallentin L. Growth differentiation factor 15 predicts all - cause morbidity and mortality in stable coronary heart disease // Clinical Chemistry. 2017. Vol. 63, no. 1. P. 325-333. doi: 10.1373/clinchem.2016.260570.Lindholm D., Hagstrom E., James S. K., Becker R. C., Cannon C. P., Himmelmann A., Katus H. A., Maurer G., Lopez-Sendon J. L., Steg P. G., Storey R. F., Siegbahn A., Wallentin L. Growth differentiation factor 15 at 1 month after an acute coronary syndrome is associated with increased risk of major bleeding // Journal of the Amercan Heart Association. 2017. Vol. 6, no. 4. P. 1-8. doi: 10.1161/JAHA.117.005580.Lindholm D., Hagstrom E., James S. K., Becker R. C., Cannon C. P., Himmelmann A., Katus H. A., Maurer G., Lopez-Sendon J. L., Steg P. G., Storey R. F., Siegbahn A., Wallentin L. Growth differentiation factor 15 at 1 month after an acute coronary syndrome is associated with increased risk of major bleeding // Journal of the Amercan Heart Association. 2017. Vol. 6, no. 4. P. 1-8. doi: 10.1161/JAHA.117.005580.Adela R., Banerjee S. K. GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective // Journal Diabetes Research. 2015. Vol. 490842. P. 1-13. doi: 10.1155/2015/490842.Adela R., Banerjee S. K. GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective // Journal Diabetes Research. 2015. Vol. 490842. P. 1-13. doi: 10.1155/2015/490842.Macia L., Tsai V. W., Nguyen A. D., Johnen H., Kuffner T., Shi Y. C., Lin S., Herzog H., Brown D. A., Breit S. N., Sainsbury A. Macrophage inhibitory cytokine 1 (MIC-1/GDF15) decreases food intake, body weight and improves glucose tolerance in mice on normal and obesogenic diets // Journal PlosOne.2012. Vol. 7, no. 4. P. 1-8. doi: 10.1371/journal.pone.0034868.Macia L., Tsai V. W., Nguyen A. D., Johnen H., Kuffner T., Shi Y. C., Lin S., Herzog H., Brown D. A., Breit S. N., Sainsbury A. Macrophage inhibitory cytokine 1 (MIC-1/GDF15) decreases food intake, body weight and improves glucose tolerance in mice on normal and obesogenic diets // Journal PlosOne.2012. Vol. 7, no. 4. P. 1-8. doi: 10.1371/journal.pone.0034868.Xu J., Kimball T. R., Lorenz J. N., Brown D. A., Bauskin A. R., Klevitsky R., Hewett T. E., Breit S. N., Molkentin J. D. GDF15/MIC-1 functions as a protective and antihypertrophic factor released from the myocardium in association with SMAD protein activation // Circulation Research. 2006. Vol. 98, no. 3. P. 342-350. doi: 10.1161/01.RES.0000202804.84885.d0.Xu J., Kimball T. R., Lorenz J. N., Brown D. A., Bauskin A. R., Klevitsky R., Hewett T. E., Breit S. N., Molkentin J. D. GDF15/MIC-1 functions as a protective and antihypertrophic factor released from the myocardium in association with SMAD protein activation // Circulation Research. 2006. Vol. 98, no. 3. P. 342-350. doi: 10.1161/01.RES.0000202804.84885.d0.Andersson-Hall U., Joelsson L., Svedin P., Mallard C., Holmang A. Growth differentiation factor 15 levels in obese and healthy pregnancies: Relation to insulin resistance and insulin secretory function // Clinical Endocrinology. 2021. Vol. 95, no. 1. P. 92-100. doi: 10.1111/cen.14433.Andersson-Hall U., Joelsson L., Svedin P., Mallard C., Holmang A. Growth differentiation factor 15 levels in obese and healthy pregnancies: Relation to insulin resistance and insulin secretory function // Clinical Endocrinology. 2021. Vol. 95, no. 1. P. 92-100. doi: 10.1111/cen.14433.Michelsen T. M., Henriksen T., Reinhold D., Powell T. L., Jansson T. The human placental proteome secreted into the maternal and fetal circulations in normal pregnancy based on 4-vessel sampling // FASEB Journal. 2019. Vol. 33, no. 2. P. 2944-2956. doi: 10.1096/fj.201801193r.Michelsen T. M., Henriksen T., Reinhold D., Powell T. L., Jansson T. The human placental proteome secreted into the maternal and fetal circulations in normal pregnancy based on 4-vessel sampling // FASEB Journal. 2019. Vol. 33, no. 2. P. 2944-2956. doi: 10.1096/fj.201801193r.Rosenfeld C. S. Sex-specific placental responses in fetal development // Endocrinology. 2015. Vol. 156, no. 10. P. 3422-3434. doi:10.1210/en.2015-1227.Rosenfeld C. S. Sex-specific placental responses in fetal development // Endocrinology. 2015. Vol. 156, no. 10. P. 3422-3434. doi:10.1210/en.2015-1227.Fejzo M. S., Trovik J., Grooten I. J., Sridharan K., Roseboom T. J., Vikanes Å., Painter R. C., Mullin P. Nausea and vomiting of pregnancy and hyperemesis gravidarum // Nature Reviews Disease Primers. 2019. Vol. 12, no. 5. P. 62-70. doi: 10.1038/s41572-019-0110-3.Fejzo M. S., Trovik J., Grooten I. J., Sridharan K., Roseboom T. J., Vikanes Å., Painter R. C., Mullin P. Nausea and vomiting of pregnancy and hyperemesis gravidarum // Nature Reviews Disease Primers. 2019. Vol. 12, no. 5. P. 62-70. doi: 10.1038/s41572-019-0110-3.Yakut K., Öcal D. F., Öztürk F. H., Öztürk M., Oğuz Y., Sınacı S., Çağlar T. Is GDF-15 level associated with gestational diabetes mellitus and adverse perinatal outcomes? // Taiwan Journal Obstet Gynecology. 2021. Vol. 60, no. 2. P. 221-224. doi: 10.1016/j.tjog.2020.12.004.Yakut K., Öcal D. F., Öztürk F. H., Öztürk M., Oğuz Y., Sınacı S., Çağlar T. Is GDF-15 level associated with gestational diabetes mellitus and adverse perinatal outcomes? // Taiwan Journal Obstet Gynecology. 2021. Vol. 60, no. 2. P. 221-224. doi: 10.1016/j.tjog.2020.12.004.Ho J. E., Mahajan A., Chen M. H., Larson M. G., McCabe E. L., Ghorbani A., Cheng S., Johnson A. D., Lindgren C. M., Kempf T., Lind L., Ingelsson E., Vasan R. S., Januzzi J., Wollert K. C., Morris A. P., Wang T. J. Clinical and genetic correlates of growth differentiation factor 15 in the community // Clinical Chemistry. 2012. Vol. 58, no. 11. P. 1582-1591. doi: 10.1373/clinchem.2012.190322.Ho J. E., Mahajan A., Chen M. H., Larson M. G., McCabe E. L., Ghorbani A., Cheng S., Johnson A. D., Lindgren C. M., Kempf T., Lind L., Ingelsson E., Vasan R. S., Januzzi J., Wollert K. C., Morris A. P., Wang T. J. Clinical and genetic correlates of growth differentiation factor 15 in the community // Clinical Chemistry. 2012. Vol. 58, no. 11. P. 1582-1591. doi: 10.1373/clinchem.2012.190322.Chrysovergis K., Wang X., Kosak J., Lee S. H., Kim J. S., Foley J. F., Travlos G., Singh S., Baek S. J., Eling T. E. NAG-1/GDF-15 prevents obesity by increasing thermogenesis, lipolysis and oxidative metabolism // International Journal of Obesity. 2014. Vol. 38, № 12. P. 1555-1564. doi: 10.1038/ijo.2014.27.Chrysovergis K., Wang X., Kosak J., Lee S. H., Kim J. S., Foley J. F., Travlos G., Singh S., Baek S. J., Eling T. E. NAG-1/GDF-15 prevents obesity by increasing thermogenesis, lipolysis and oxidative metabolism // International Journal of Obesity. 2014. Vol. 38, № 12. P. 1555-1564. doi: 10.1038/ijo.2014.27.Marjono A. B., Brown D. A., Horton K. E., Wallace E. M., Breit S. N., Manuelpillai U. Macrophage inhibitory cytokine-1 in gestational tissues and maternal serum in normal and pre-eclamptic pregnancy // Placenta. 2003. Vol. 24, no. 1. P. 100-106. doi: 10.1053/plac.2002.0881.Marjono A. B., Brown D. A., Horton K. E., Wallace E. M., Breit S. N., Manuelpillai U. Macrophage inhibitory cytokine-1 in gestational tissues and maternal serum in normal and pre-eclamptic pregnancy // Placenta. 2003. Vol. 24, no. 1. P. 100-106. doi: 10.1053/plac.2002.0881.Chen Q., Wang Y., Zhao M., Hyett J., da Silva C. F., Nie G. Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases // Cytokine. 2016. Vol. 83. P. 226-230. doi: 10.1016/j.cyto.2016.0.Chen Q., Wang Y., Zhao M., Hyett J., da Silva C. F., Nie G. Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases // Cytokine. 2016. Vol. 83. P. 226-230. doi: 10.1016/j.cyto.2016.0.Sugulle M., Dechend R., Herse F., Weedon-Fekjaer M. S., Johnsen G. M., Brosnihan K. B., Anton L., Luft F. C., Wollert K. C., Kempf T., Staff A. C. Circulating and placental growth-differentiation factor 15 in preeclampsia and in pregnancy complicated by diabetes mellitus // Hypertension. 2009. Vol. 54. P. 106-112. doi: 10.1161/HYPERTENSIONAHA.109.130583.Sugulle M., Dechend R., Herse F., Weedon-Fekjaer M. S., Johnsen G. M., Brosnihan K. B., Anton L., Luft F. C., Wollert K. C., Kempf T., Staff A. C. Circulating and placental growth-differentiation factor 15 in preeclampsia and in pregnancy complicated by diabetes mellitus // Hypertension. 2009. Vol. 54. P. 106-112. doi: 10.1161/HYPERTENSIONAHA.109.130583.Temel Yuksel I., Mathyk B. A., Aslan Cetin B., Turhan U., Okumus Z. G., Yetkin Yildirim G., Acar D. K. Maternal levels of growth differentiation factor-15 in patients with preeclampsia // Hypertens Pregnancy. 2018. Vol. 37, no. 4. P. 192-196. doi: 10.1080/10641955.2018.1524477.Temel Yuksel I., Mathyk B. A., Aslan Cetin B., Turhan U., Okumus Z. G., Yetkin Yildirim G., Acar D. K. Maternal levels of growth differentiation factor-15 in patients with preeclampsia // Hypertens Pregnancy. 2018. Vol. 37, no. 4. P. 192-196. doi: 10.1080/10641955.2018.1524477.Cruickshank T., MacDonald T. M., Walker S. P., Keenan E., Dane K., Middleton A., Kyritsis V., Myers J., Cluver C., Hastie R., Bergman L., Garcha D., Cannon P., Murray E., Nguyen T. V., Hiscock R., Pritchard N., Hannan N. J., Tong S., Kaitu'u-Lino T. J. Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker // Journal of the American Heart Association. 2021. Vol. 10, no. 16. P. 1-12. doi: 10.1161/JAHA.120.020302.Cruickshank T., MacDonald T. M., Walker S. P., Keenan E., Dane K., Middleton A., Kyritsis V., Myers J., Cluver C., Hastie R., Bergman L., Garcha D., Cannon P., Murray E., Nguyen T. V., Hiscock R., Pritchard N., Hannan N. J., Tong S., Kaitu'u-Lino T. J. Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker // Journal of the American Heart Association. 2021. Vol. 10, no. 16. P. 1-12. doi: 10.1161/JAHA.120.020302.Skubisz M. M., Brown J. K., Tong S., Kaitu’u-Lino T., Horne A. W. Maternal Serum Macrophage Inhibitory Cytokine-1 as a Biomarker for Ectopic Pregnancy in Women with a Pregnancy of Unknown Location // PloS One. 2013. Vol. 8, no. 6. P. 1-5. doi: 10.1371/journal.pone.0066339.Skubisz M. M., Brown J. K., Tong S., Kaitu’u-Lino T., Horne A. W. Maternal Serum Macrophage Inhibitory Cytokine-1 as a Biomarker for Ectopic Pregnancy in Women with a Pregnancy of Unknown Location // PloS One. 2013. Vol. 8, no. 6. P. 1-5. doi: 10.1371/journal.pone.0066339.Soucek K., Slabakova E., Ovesna P., Malenovska A., Kozubik A., Hampl A. Growth/differentiation factor-15 is an abundant cytokine in human seminal plasma // Human Reproduction. 2010. Vol. 25. P. 2962-2971.Soucek K., Slabakova E., Ovesna P., Malenovska A., Kozubik A., Hampl A. Growth/differentiation factor-15 is an abundant cytokine in human seminal plasma // Human Reproduction. 2010. Vol. 25. P. 2962-2971.Tong S., Ngian G. L., Onwude J. L., Permezel M., Saglam B., Hay S., Konje J. C., Marczylo T. H., Fleming G., Walker S. P., Lappas M. Diagnostic accuracy of maternal serum macrophage inhibitory cytokine-1 and pregnancy-associated plasma protein-A at 6-10 weeks of gestation to predict miscarriage // Obstetrics Gynecology. 2012. Vol. 119, no. 5. P. 1000-1008. doi: 10.1097/AOG.0b013e3182518fd3.Tong S., Ngian G. L., Onwude J. L., Permezel M., Saglam B., Hay S., Konje J. C., Marczylo T. H., Fleming G., Walker S. P., Lappas M. Diagnostic accuracy of maternal serum macrophage inhibitory cytokine-1 and pregnancy-associated plasma protein-A at 6-10 weeks of gestation to predict miscarriage // Obstetrics Gynecology. 2012. Vol. 119, no. 5. P. 1000-1008. doi: 10.1097/AOG.0b013e3182518fd3.

The authors declare that there are no conflicts of interest present.