unojУспехи наук о животныхErnst Journal of Animal Science3034-493ХФедеральный исследовательский центр животноводства – ВИЖ имени академика Л.К. Эрнста10.25687/3034-493X.2026.6.1.004unoj-38Research ArticleЗООТЕХНИЯ И ВЕТЕРИНАРИЯANIMAL AND VETERINARY SCIENCEМикроРНК экзосом молока как эпигенетический маркер метаболизма и мастита у коровMilk exosomal microRNA as an epigenetic marker of metabolism and mastitis in cowsБарковаО. Ю.BarkovaO. Yu.

Санкт-Петербург

Saint Petersburg

ВНИИГРЖ — филиал ФГБНУ ФИЦ ВИЖ им. Л.К. ЭрнстаAll-Russian Research Institute of Genetics and Farm Animal Breeding, Branch of L.K. Ernst Federal Research Center for Animal Husbandry202622042026015874Copyright © Баркова О.Ю., 20262026Баркова О.Ю.Barkova O.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.ernstjournal.ru/jour/article/view/38

Молоко как важнейший источник питания содержит широко известные белки, минералы, витамины и менее известные сигнальные молекулы в виде коротких некодирующих РНК как в свободном виде, так и содержащихся в экзосомах. Состав экзосомального груза динамичен и зависит от физиологического состояния организма, включая стадию лактации и здоровье молочной железы. Данный обзор посвящен теме таких ключевых эпигенетических компонентов, как микроРНК молока, заключенных в экзосомах. В обзоре рассмотрены представления о роли экзосомных микроРНК молока как генетического маркера продуктивности и здоровья молочного скота. Затронута тема формирования экзосом и механизм сортировки экзосомных грузов, большое внимание уделяется этапам биосинтеза микроРНК у млекопитающих и механизма воздействия на геном как главного эпигенетического посттранскрипционного фактора. Описаны работы по изучению профиля микроРНК молока в зависимости от стадии лактации и состояния здоровья молочной железы крупного рогатого скота. Представленные данные будут полезны для понимания организации, регуляции и эпигенетики микроРНК в молоке жвачных животных и открыва.т возможности для разработки новых диагностических и селекционных инструментов в животноводстве.

Milk, a vital source of nutrition, contains well-known proteins, minerals, vitamins, and lesser-known signaling molecules in the form of short non-coding RNAs, both free and contained in exosomes. The composition of the exosomal load is dynamic and depends on the physiological state of the organism, including the stage of lactation and mammary gland health. This review focuses on key epigenetic components such as milk microRNAs contained in exosomes. This review examines the role of milk exosomal microRNAs as a genetic marker of productivity and health in dairy cattle. It addresses the formation of exosomes and the mechanism of exosomal cargo sorting, focusing on the stages of microRNA biosynthesis in mammals and the mechanism of their influence on the genome as the main epigenetic post-transcription factor. Studies on the profile of milk microRNAs depending on the stage of lactation and mammary gland health in cattle are described. The presented data will be useful for understanding the organization, regulation and epigenetics of microRNAs in ruminant milk and opens up opportunities for the development of new diagnostic and selection tools in animal husbandry.

микроРНКэкзосомымолокожвачныемаститmicroRNAexosomesmilkruminantsmastitisИсследование выполнено при финансовой поддержке программы государственного задания Российской Федерации № FGGN-2024-0015ReferencesKosaka N. et al. MicroRNA as a new immune-regulatory agent in breast milk // Silence. 2010b. Vol. 251. P. 7. doi:10.1186/1758-907X-1-7.Kosaka N. et al. MicroRNA as a new immune-regulatory agent in breast milk // Silence. 2010b. Vol. 251. P. 7. doi:10.1186/1758-907X-1-7.Zhou Q. et al. Immune-related microRNAs are abundant in breast milk exosomes // Int. J. Biol. Sci. 2012. Vol. 8. P. 118 – 123. doi.org/10.7150/ijbs.8.118.Zhou Q. et al. Immune-related microRNAs are abundant in breast milk exosomes // Int. J. Biol. Sci. 2012. Vol. 8. P. 118 – 123. doi.org/10.7150/ijbs.8.118.Munch E.M. et al. Transcriptome profiling of microRNA by next-gen deep sequencing reveals known and novel microRNAs species in the lipid fraction of human breast milk // PLoS ONE. 2013. Vol. 8. P. 50564. https://doi.org/10.1371/journal.pone.0050564.Munch E.M. et al. Transcriptome profiling of microRNA by next-gen deep sequencing reveals known and novel microRNAs species in the lipid fraction of human breast milk // PLoS ONE. 2013. Vol. 8. P. 50564. https://doi.org/10.1371/journal.pone.0050564.Izumi H. et al. Bovine milk contains microRNA and messenger RNA that are stable under degradative conditions // J. Dairy Sci. 2012. Vol. 9. P. 4831 – 4841. https://doi.org/10.3168/jds.2012-5489.Izumi H. et al. Bovine milk contains microRNA and messenger RNA that are stable under degradative conditions // J. Dairy Sci. 2012. Vol. 9. P. 4831 – 4841. https://doi.org/10.3168/jds.2012-5489.Cendron F. et al. Analysis of miRNAs in milk of four livestock species // BMC genomics. 2024. Vol. 25. № 1. P. 859. https://doi.org/10.1186/s12864-024-10783-4.Cendron F. et al. Analysis of miRNAs in milk of four livestock species // BMC genomics. 2024. Vol. 25. № 1. P. 859. https://doi.org/10.1186/s12864-024-10783-4.Lässer C. et al. Human saliva, plasma and breast milk exosomes contain RNA: Uptake by macrophages // J. Transl. Med. 2011. Vol. 9. P. 9. https://doi.org/10.1186/1479-5876-9-9.Lässer C. et al. Human saliva, plasma and breast milk exosomes contain RNA: Uptake by macrophages // J. Transl. Med. 2011. Vol. 9. P. 9. https://doi.org/10.1186/1479-5876-9-9.Chen X. et al. Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products // Cell Res. 2010. Vol. 20. P. 1128 – 1137. https://doi.org/10.1038/cr.2010.80.Chen X. et al. Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products // Cell Res. 2010. Vol. 20. P. 1128 – 1137. https://doi.org/10.1038/cr.2010.80.Doyle L.M., Wang M.Z. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis // Cells. 2019. Vol. 8. № 7. P. 727. https://doi.org/10.3390/cells8070727.Doyle L.M., Wang M.Z. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis // Cells. 2019. Vol. 8. № 7. P. 727. https://doi.org/10.3390/cells8070727.Zhang J. et al. Exosome and exosomal microRNA: trafficking, sorting, and function // Genomics Proteomics Bioinformatics. 2015. Vol. 13. № 1. P. 17 – 24. https://doi.org/10.1016/j.gpb.2015.02.001.Zhang J. et al. Exosome and exosomal microRNA: trafficking, sorting, and function // Genomics Proteomics Bioinformatics. 2015. Vol. 13. № 1. P. 17 – 24. https://doi.org/10.1016/j.gpb.2015.02.001.Charga E.; West R. The biological significance of the thromboplastic protein of blood // J. Biol. Chem. 1946. Vol. 166. P. 189 – 197.Charga E.; West R. The biological significance of the thromboplastic protein of blood // J. Biol. Chem. 1946. Vol. 166. P. 189 – 197.Wolf P. The nature and significance of platelet products in human plasma // Br. J. Haematol. 1967. Vol. 13. P. 269 – 288.Wolf P. The nature and significance of platelet products in human plasma // Br. J. Haematol. 1967. Vol. 13. P. 269 – 288.Pan B.T., Johnstone R. Selective externalization of the transferrin receptor by sheep reticulocytes in vitro. Response to ligands and inhibitors of endocytosis // J. Biol. Chem. 1984. Vol. 259. P. 9776 – 9782.Pan B.T., Johnstone R. Selective externalization of the transferrin receptor by sheep reticulocytes in vitro. Response to ligands and inhibitors of endocytosis // J. Biol. Chem. 1984. Vol. 259. P. 9776 – 9782.Pan B.T., Johnstone R.M. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor // Cell. 1983. Vol. 33. P. 967 – 978. https://doi.org/10.1016/0092-8674(83)90040-5.Pan B.T., Johnstone R.M. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor // Cell. 1983. Vol. 33. P. 967 – 978. https://doi.org/10.1016/0092-8674(83)90040-5.Johnstone R.M., Bianchini A., Teng K. Reticulocyte maturation and exosome release: transferrin receptor containing exosomes shows multiple plasma membrane functions // Blood. 1989. Vol. 74. P. 1844 – 1851.Johnstone R.M., Bianchini A., Teng K. Reticulocyte maturation and exosome release: transferrin receptor containing exosomes shows multiple plasma membrane functions // Blood. 1989. Vol. 74. P. 1844 – 1851.Mathivanan S., Ji H. Simpson R.J. Exosomes: extracellular organelles important in intercellular communication // J. Proteomics. 2010. Vol. 73. P. 1907 – 1920. https://doi.org/10.1016/j.jprot.2010.06.006.Mathivanan S., Ji H. Simpson R.J. Exosomes: extracellular organelles important in intercellular communication // J. Proteomics. 2010. Vol. 73. P. 1907 – 1920. https://doi.org/10.1016/j.jprot.2010.06.006.Gross J.C. et al. Active Wnt proteins are secreted on exosomes // Nat Cell Biol. 2012. Vol. 14. P. 1036 – 1045. https://doi.org/10.1038/ncb2574.Gross J.C. et al. Active Wnt proteins are secreted on exosomes // Nat Cell Biol. 2012. Vol. 14. P. 1036 – 1045. https://doi.org/10.1038/ncb2574.Pieters B.C. et al. Commercial cow milk contains physically stable extracellular vesicles expressing immunoregulatory TGF-beta // PLoS ONE. 2015. Vol. 10. P. 121 – 123. https://doi.org/10.1371/journal.pone.0121123.Pieters B.C. et al. Commercial cow milk contains physically stable extracellular vesicles expressing immunoregulatory TGF-beta // PLoS ONE. 2015. Vol. 10. P. 121 – 123. https://doi.org/10.1371/journal.pone.0121123.Melnik B.C. et al. Milk микроРНК: Simple nutrients or systemic functional regulators? // Nutr. Metab. 2016. Vol. 13. № 42. https://doi.org/10.1186/s12986-016-0101-2.Melnik B.C. et al. Milk микроРНК: Simple nutrients or systemic functional regulators? // Nutr. Metab. 2016. Vol. 13. № 42. https://doi.org/10.1186/s12986-016-0101-2.Almughlliq F.B. et al. Circulating exosomes may identify biomarkers for cows at risk for metabolic dysfunction // Sci. Rep. 2019. Vol. 9. № 1. P. 13879. https://doi.org/10.1038/s41598-019-50244-7.Almughlliq F.B. et al. Circulating exosomes may identify biomarkers for cows at risk for metabolic dysfunction // Sci. Rep. 2019. Vol. 9. № 1. P. 13879. https://doi.org/10.1038/s41598-019-50244-7.Mitchell M.D. et al. Plasma exosome profiles from dairy cows with divergent fertility phenotypes // J. Dairy Sci. 2016. Vol. 99. P. 7590 – 7601. https://doi.org/10.3168/jds.2016-11060.Mitchell M.D. et al. Plasma exosome profiles from dairy cows with divergent fertility phenotypes // J. Dairy Sci. 2016. Vol. 99. P. 7590 – 7601. https://doi.org/10.3168/jds.2016-11060.Zhang Y. et al. Exosomes: Biogenesis, biologic function and clinical potential //Cell Biosci. 2019. Vol. 9. P. 19. https://doi.org/10.1186/s13578-019-0282-2.Zhang Y. et al. Exosomes: Biogenesis, biologic function and clinical potential //Cell Biosci. 2019. Vol. 9. P. 19. https://doi.org/10.1186/s13578-019-0282-2.Henne W.M., Buchkovich N.J., Emr S.D. The ESCRT pathway // Dev. Cell. 2011. Vol. 21. P. 77 – 91. https://doi.org/10.1016/j.devcel.2011.05.015.Henne W.M., Buchkovich N.J., Emr S.D. The ESCRT pathway // Dev. Cell. 2011. Vol. 21. P. 77 – 91. https://doi.org/10.1016/j.devcel.2011.05.015.Hurley J.H. ESCRTs are everywhere // EMBO J. 2015. Vol. 34. P. 2398 – 2407. https://doi.org/10.15252/embj.201592484.Hurley J.H. ESCRTs are everywhere // EMBO J. 2015. Vol. 34. P. 2398 – 2407. https://doi.org/10.15252/embj.201592484.Perez-Hernandez D. et al. The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes // J. Biol Chem. 2013. Vol. 288. P. 11649 – 11661. https://doi.org/10.1074/jbc.M112.445304.Perez-Hernandez D. et al. The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes // J. Biol Chem. 2013. Vol. 288. P. 11649 – 11661. https://doi.org/10.1074/jbc.M112.445304.Van den Boorn J.G. et al. Exosomes as nucleic acid nanocarriers // Adv. Drug Deliv. Rev. 2013. Vol. 65. P. 331 – 335. https://doi.org/10.1016/j.addr.2012.06.011.Van den Boorn J.G. et al. Exosomes as nucleic acid nanocarriers // Adv. Drug Deliv. Rev. 2013. Vol. 65. P. 331 – 335. https://doi.org/10.1016/j.addr.2012.06.011.Villarroya-Beltri C. et al. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs // Nature communications. 2013. № 4. Р. 2980. https://doi.org/10.1038/ncomms3980.Villarroya-Beltri C. et al. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs // Nature communications. 2013. № 4. Р. 2980. https://doi.org/10.1038/ncomms3980.Santangelo L. et al. The RNA-Binding Protein SYNCRIP Is a Component of the Hepatocyte Exosomal Machinery Controlling MicroRNA Sorting // Cell reports. 2016. Vol. 17. № 3. P. 799 – 808. https://doi.org/10.1016/j.celrep.2016.09.031.Santangelo L. et al. The RNA-Binding Protein SYNCRIP Is a Component of the Hepatocyte Exosomal Machinery Controlling MicroRNA Sorting // Cell reports. 2016. Vol. 17. № 3. P. 799 – 808. https://doi.org/10.1016/j.celrep.2016.09.031.Shurtleff M.J. et al. Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction // Elife. 2016. Vol. 25. № 5. Р. e19276. https://doi.org/10.7554/eLife.19276.Shurtleff M.J. et al. Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction // Elife. 2016. Vol. 25. № 5. Р. e19276. https://doi.org/10.7554/eLife.19276.Ostrowski M. et al. Rab27a and Rab27b control different steps of the exosome secretion pathway // Nat Cell Biol. 2010. Vol. 12. № 1. P. 19 – 30. https://doi.org/10.1038/ncb2000.Ostrowski M. et al. Rab27a and Rab27b control different steps of the exosome secretion pathway // Nat Cell Biol. 2010. Vol. 12. № 1. P. 19 – 30. https://doi.org/10.1038/ncb2000.Michlewski G., Cáceres J.F. Post-transcriptional control of microRNA biogenesis // RNA. 2019. Vol. 25. № 1. P. 1 – 16. https://doi.org/10.1261/rna.068692.118.Michlewski G., Cáceres J.F. Post-transcriptional control of microRNA biogenesis // RNA. 2019. Vol. 25. № 1. P. 1 – 16. https://doi.org/10.1261/rna.068692.118.Mohr A.M., Mott J.L. Overview of microRNA biology // Semin Liver Dis. 2015. Vol. 35. № 1. P. 3 – 11. https://doi.org/10.1055/s-0034-1397344.Mohr A.M., Mott J.L. Overview of microRNA biology // Semin Liver Dis. 2015. Vol. 35. № 1. P. 3 – 11. https://doi.org/10.1055/s-0034-1397344.Lee Y. et al. The nuclear RNase III Drosha initiates microRNA processing // Nature. 2003. Vol. 425. P. 415 – 419. https://doi.org/10.1038/nature01957.Lee Y. et al. The nuclear RNase III Drosha initiates microRNA processing // Nature. 2003. Vol. 425. P. 415 – 419. https://doi.org/10.1038/nature01957.Ketting R.F. et al. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans // Genes Dev. 2001. Vol. 15. P. 2654 – 2659. https://doi.org/10.1101/gad.927801.Ketting R.F. et al. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans // Genes Dev. 2001. Vol. 15. P. 2654 – 2659. https://doi.org/10.1101/gad.927801.Kobayashi H., Tomari Y. RISC assembly: coordination between small RNAs and Argonaute proteins // Biochim Biophys Acta. 2016. Vol. 1859. P. 71 – 81. https://doi.org/10.1016/j.bbagrm.2015.08.007.Kobayashi H., Tomari Y. RISC assembly: coordination between small RNAs and Argonaute proteins // Biochim Biophys Acta. 2016. Vol. 1859. P. 71 – 81. https://doi.org/10.1016/j.bbagrm.2015.08.007.Bartel D.P. MicroRNAs: target recognition and regulatory functions // Cell. 2009. Vol. 136. № 2. P. 215 – 233. https://doi.org/10.1016/j.cell.2009.01.002.Bartel D.P. MicroRNAs: target recognition and regulatory functions // Cell. 2009. Vol. 136. № 2. P. 215 – 233. https://doi.org/10.1016/j.cell.2009.01.002.Vasudevan S., Tong Y., Steitz J.A. Switching from repression to activation: microRNAs can up-regulate translation // Science. 2007. Vol. 318. № 5858. P. 1931 – 1934. https://doi.org/10.1126/science.1149460.Vasudevan S., Tong Y., Steitz J.A. Switching from repression to activation: microRNAs can up-regulate translation // Science. 2007. Vol. 318. № 5858. P. 1931 – 1934. https://doi.org/10.1126/science.1149460.Dykxhoorn D.M., Novina C.D., Sharp P.A. Killing the messenger: short RNAs that silence gene expression // Nat Rev Mol Cell Biol. 2003. Vol. 4. № 6. P. 457 – 467. https://doi.org/10.1038/nrm1129.Dykxhoorn D.M., Novina C.D., Sharp P.A. Killing the messenger: short RNAs that silence gene expression // Nat Rev Mol Cell Biol. 2003. Vol. 4. № 6. P. 457 – 467. https://doi.org/10.1038/nrm1129.Baek D. et al. The impact of microRNAs on protein output // Nature. 2008. Vol. 455. № 7209. P. 64 – 71. https://doi.org/10.1038/nature07242.Baek D. et al. The impact of microRNAs on protein output // Nature. 2008. Vol. 455. № 7209. P. 64 – 71. https://doi.org/10.1038/nature07242.Selbach M. et al. Widespread changes in protein synthesis induced by microRNAs // Nature. 2008. Vol. 455. № 7209. P. 58 – 63. https://doi.org/10.1038/nature07228.Selbach M. et al. Widespread changes in protein synthesis induced by microRNAs // Nature. 2008. Vol. 455. № 7209. P. 58 – 63. https://doi.org/10.1038/nature07228.Guo H. et al. Mammalian microRNAs predominantly act to decrease target mRNA levels // Nature. 2010. Vol. 466. № 7308. P. 835 – 840. https://doi.org/10.1038/nature09267.Guo H. et al. Mammalian microRNAs predominantly act to decrease target mRNA levels // Nature. 2010. Vol. 466. № 7308. P. 835 – 840. https://doi.org/10.1038/nature09267.Reinhart B.J. et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans // Nature. 2000. Vol. 403. № 6772. P. 901 – 906. https://doi.org/10.1038/35002607.Reinhart B.J. et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans // Nature. 2000. Vol. 403. № 6772. P. 901 – 906. https://doi.org/10.1038/35002607.Place R.F. et al. MicroRNA-373 induces expression of genes with complementary promoter sequences // Proc Natl Acad Sci U S A. 2008. Vol. 105. № 5. P. 1608 – 1613. https://doi.org/10.1073/pnas.0707594105.Place R.F. et al. MicroRNA-373 induces expression of genes with complementary promoter sequences // Proc Natl Acad Sci U S A. 2008. Vol. 105. № 5. P. 1608 – 1613. https://doi.org/10.1073/pnas.0707594105.Ishikawa H. et al. mRNA profile in milk extracellular vesicles from bovine leukemia virus-infected cattle // Viruses. 2020. Vol. 12. P. 669. https://doi.org/10.3390/v12060669.Ishikawa H. et al. mRNA profile in milk extracellular vesicles from bovine leukemia virus-infected cattle // Viruses. 2020. Vol. 12. P. 669. https://doi.org/10.3390/v12060669.Chen T. et al. Revelation of mRNAs and proteins in porcine milk exosomes by transcriptomic and proteomic analysis // BMC Vet. Res. 2017. Vol. 13. P. 101. https://doi.org/10.1186/s12917-017-1021-8.Chen T. et al. Revelation of mRNAs and proteins in porcine milk exosomes by transcriptomic and proteomic analysis // BMC Vet. Res. 2017. Vol. 13. P. 101. https://doi.org/10.1186/s12917-017-1021-8.Izumi H. et al. Bovine milk exosomes contain microRNA and mRNA and are taken up by human macrophages // J. Dairy Sci. 2015. Vol. 98. P. 2920 – 2933. https://doi.org/10.3168/jds.2014-9076.Izumi H. et al. Bovine milk exosomes contain microRNA and mRNA and are taken up by human macrophages // J. Dairy Sci. 2015. Vol. 98. P. 2920 – 2933. https://doi.org/10.3168/jds.2014-9076.Tabet F. et al. HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells // Nat Commun. 2014. Vol. 5. P.3292. https://doi.org/10.1038/ncomms4292.Tabet F. et al. HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells // Nat Commun. 2014. Vol. 5. P.3292. https://doi.org/10.1038/ncomms4292.Vickers K.C. et al. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins // Nat Cell Biol. 2011. Vol. 13. P. 423 – 33. https://doi.org/10.1038/ncb2210.Vickers K.C. et al. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins // Nat Cell Biol. 2011. Vol. 13. P. 423 – 33. https://doi.org/10.1038/ncb2210.Arroyo J.D. et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma // Proc Natl Acad Sci U S A. 2011. Vol. 108. P. 5003 – 5008. https://doi.org/10.1073/pnas.1019055108.Arroyo J.D. et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma // Proc Natl Acad Sci U S A. 2011. Vol. 108. P. 5003 – 5008. https://doi.org/10.1073/pnas.1019055108.Hata T. et al. Isolation of bovine milk-derived microvesicles carrying mRNAs and microRNAs // Biochem. Biophys. Res. Commun. 2010. Vol. 396. P. 528 – 533. https://doi.org/10.1016/j.bbrc.2010.04.135.Hata T. et al. Isolation of bovine milk-derived microvesicles carrying mRNAs and microRNAs // Biochem. Biophys. Res. Commun. 2010. Vol. 396. P. 528 – 533. https://doi.org/10.1016/j.bbrc.2010.04.135.Howard K.M. et al. Loss of microRNAs during processing and storage of cow’s (Bos taurus) milk // J. Agric. Food Chem. 2015. Vol. 63. P. 588 – 592. https://doi.org/10.1021/jf505526w.Howard K.M. et al. Loss of microRNAs during processing and storage of cow’s (Bos taurus) milk // J. Agric. Food Chem. 2015. Vol. 63. P. 588 – 592. https://doi.org/10.1021/jf505526w.Sun Q. et al. Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum // Protein Cell. 2013. Vol. 4. P. 197 – 210. https://doi.org/10.1007/s13238-013-2119-9.Sun Q. et al. Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum // Protein Cell. 2013. Vol. 4. P. 197 – 210. https://doi.org/10.1007/s13238-013-2119-9.Klopfleisch R., Weiss A.T., Gruber A.D. Excavation of a buried treasure–DNA, mRNA, microRNA and protein analysis in formalin fixed, paran embedded tissues // Histol. Histopathol. 2011. Vol. 26. P. 797 – 810. https://doi.org/10.14670/HH-26.797.Klopfleisch R., Weiss A.T., Gruber A.D. Excavation of a buried treasure–DNA, mRNA, microRNA and protein analysis in formalin fixed, paran embedded tissues // Histol. Histopathol. 2011. Vol. 26. P. 797 – 810. https://doi.org/10.14670/HH-26.797.Streichert T., Otto B., Lehmann U. MicroRNA expression profiling in archival tissue specimens: Methods and data processing // Mol. Biotechnol. 2012. Vol. 50. P. 159 – 169. https://doi.org/10.1007/s12033-011-9427-1.Streichert T., Otto B., Lehmann U. MicroRNA expression profiling in archival tissue specimens: Methods and data processing // Mol. Biotechnol. 2012. Vol. 50. P. 159 – 169. https://doi.org/10.1007/s12033-011-9427-1.Srikok S. et al. Potential role of MicroRNA as a diagnostic tool in the detection of bovine mastitis // Prev. Vet. Med. 2020. Vol. 182. P. 101 – 105. https://doi.org/10.1016/j.prevetmed.2020.105101.Srikok S. et al. Potential role of MicroRNA as a diagnostic tool in the detection of bovine mastitis // Prev. Vet. Med. 2020. Vol. 182. P. 101 – 105. https://doi.org/10.1016/j.prevetmed.2020.105101.Bu D.P. et al. Identification and characterization of microRNA sequences from bovine mammary epithelial cells // J. Dairy Sci. 2015. Vol. 98. № 3. P. 1696 – 705. https://doi.org/10.3168/jds.2014-8217.Bu D.P. et al. Identification and characterization of microRNA sequences from bovine mammary epithelial cells // J. Dairy Sci. 2015. Vol. 98. № 3. P. 1696 – 705. https://doi.org/10.3168/jds.2014-8217.Bourdon C. et al. RumimiR: A detailed microRNA database focused on ruminant species // Database. 2019. baz099. https://10.1093/database/baz099.Bourdon C. et al. RumimiR: A detailed microRNA database focused on ruminant species // Database. 2019. baz099. https://10.1093/database/baz099.Li Z. et al. Expression profiles of microRNAs from lactating and non-lactating bovine mammary glands and identification of microRNA related to lactation // BMC Genomics. 2012b. Vol. 13. P. 731. https://doi.org/10.1186/1471-2164-13-731.Li Z. et al. Expression profiles of microRNAs from lactating and non-lactating bovine mammary glands and identification of microRNA related to lactation // BMC Genomics. 2012b. Vol. 13. P. 731. https://doi.org/10.1186/1471-2164-13-731.Shen B., Zhang L., Lian C. Deep Sequencing and Screening of Differentially Expressed MicroRNAs Related to Milk Fat Metabolism in Bovine Primary Mammary Epithelial Cells // Int. J. Mol. Sci. 2016. Vol. 17. P. 200. https://doi.org/10.3390/ijms17020200.Shen B., Zhang L., Lian C. Deep Sequencing and Screening of Differentially Expressed MicroRNAs Related to Milk Fat Metabolism in Bovine Primary Mammary Epithelial Cells // Int. J. Mol. Sci. 2016. Vol. 17. P. 200. https://doi.org/10.3390/ijms17020200.Li R. et al. Transcriptome microRNA profiling of bovine mammary glands infected with Staphylococcus aureus // Int. J. Mol. Sci. 2015. Vol. 16. P. 4997 – 5013. https://doi.org/10.3390/ijms16034997.Li R. et al. Transcriptome microRNA profiling of bovine mammary glands infected with Staphylococcus aureus // Int. J. Mol. Sci. 2015. Vol. 16. P. 4997 – 5013. https://doi.org/10.3390/ijms16034997.Cui X. et al. Comprehensive MicroRNA Expression Profile of the Mammary Gland in Lactating Dairy Cows With Extremely Different Milk Protein and Fat Percentages // Front Genet. 2020. Vol. 3. № 11. P. 548268. https://doi.org/10.3389/fgene.2020.548268.Cui X. et al. Comprehensive MicroRNA Expression Profile of the Mammary Gland in Lactating Dairy Cows With Extremely Different Milk Protein and Fat Percentages // Front Genet. 2020. Vol. 3. № 11. P. 548268. https://doi.org/10.3389/fgene.2020.548268.Bonci D. et al. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities // Nat. Med. 2008. Vol. 14. P. 1271 – 1277. https://doi.org/10.1038/nm.1880.Bonci D. et al. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities // Nat. Med. 2008. Vol. 14. P. 1271 – 1277. https://doi.org/10.1038/nm.1880.Bandi N. et al. miR-15a and miR-16 are implicated in cell cycle regulation in a Rb-dependent manner and are frequently deleted or downregulated in non-small cell lung cancer // Cancer Res. 2009. № 69. P. 5553 – 5559. https://doi.org/.10.1158/0008-5472.can-08-4277.Bandi N. et al. miR-15a and miR-16 are implicated in cell cycle regulation in a Rb-dependent manner and are frequently deleted or downregulated in non-small cell lung cancer // Cancer Res. 2009. № 69. P. 5553 – 5559. https://doi.org/.10.1158/0008-5472.can-08-4277.Cimmino A. et al. miR-15 and miR-16 induce apoptosis by targeting BCL2 // Proc. Natl. Acad. Sci. U S A. 2005. Vol. 102. P. 13944 – 13949. https://doi.org/10.1073/pnas.0506654102.Cimmino A. et al. miR-15 and miR-16 induce apoptosis by targeting BCL2 // Proc. Natl. Acad. Sci. U S A. 2005. Vol. 102. P. 13944 – 13949. https://doi.org/10.1073/pnas.0506654102.Aqeilan R.I., Calin G.A., Croce C.M. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives // Cell Death Differ. 2010. Vol. 17. P. 215 – 220. https://doi.org/10.1038/cdd.2009.69.Aqeilan R.I., Calin G.A., Croce C.M. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives // Cell Death Differ. 2010. Vol. 17. P. 215 – 220. https://doi.org/10.1038/cdd.2009.69.Li H.M., Wang C.M., Li Q.Z., Gao X.J. MiR-15a decreases bovine mammary epithelial cell viability and lactation and regulates growth hormone receptor expression // Molecules. 2012a. Vol. 17. P. 12037 – 12048.https://doi.org/10.3390/molecules171012037.Li H.M., Wang C.M., Li Q.Z., Gao X.J. MiR-15a decreases bovine mammary epithelial cell viability and lactation and regulates growth hormone receptor expression // Molecules. 2012a. Vol. 17. P. 12037 – 12048.https://doi.org/10.3390/molecules171012037.Cui X. et al. Transcriptional profiling of mammary gland in Holstein cows with extremely different milk protein and fat percentage using RNA sequencing // BMC Genomics. 2014. Vol. 15. P. 226. https://doi.org/10.1186/1471-2164-15-226.Cui X. et al. Transcriptional profiling of mammary gland in Holstein cows with extremely different milk protein and fat percentage using RNA sequencing // BMC Genomics. 2014. Vol. 15. P. 226. https://doi.org/10.1186/1471-2164-15-226.Billa P.A. et al. Deep RNA-Seq reveals miRNome differences in mammary tissue of lactating Holstein and Montbéliarde cows // BMC Genomics. 2019. Vol. 20. P. 621. https://doi.org/10.1186/s12864-019-5987-4.Billa P.A. et al. Deep RNA-Seq reveals miRNome differences in mammary tissue of lactating Holstein and Montbéliarde cows // BMC Genomics. 2019. Vol. 20. P. 621. https://doi.org/10.1186/s12864-019-5987-4.Laplante M., Sabatini D.M. An emerging role of mTOR in lipid biosynthesis // Curr. Biol. 2009. Vol. 19. P. 1046 – 1052. https://doi.org/10.1016/j.cub.2009.09.058.Laplante M., Sabatini D.M. An emerging role of mTOR in lipid biosynthesis // Curr. Biol. 2009. Vol. 19. P. 1046 – 1052. https://doi.org/10.1016/j.cub.2009.09.058.Melnik B.C., Schmitz G. MicroRNAs: Milk's epigenetic regulators.// Best Pract Res Clin Endocrinol Metab. 2017. Vol. 31. № 4. P. 427 – 442. https://doi.org/10.1016/j.beem.2017.10.003.Melnik B.C., Schmitz G. MicroRNAs: Milk's epigenetic regulators.// Best Pract Res Clin Endocrinol Metab. 2017. Vol. 31. № 4. P. 427 – 442. https://doi.org/10.1016/j.beem.2017.10.003.Wang J. et al. MicroRNA-152 regulates DNA methyltransferase 1 and is involved in the development and lactation of mammary glands in dairy cows // PLoS One. 2014. Vol. 9. P. 101358. https://doi.org/10.1371/journal.pone.0101358.Wang J. et al. MicroRNA-152 regulates DNA methyltransferase 1 and is involved in the development and lactation of mammary glands in dairy cows // PLoS One. 2014. Vol. 9. P. 101358. https://doi.org/10.1371/journal.pone.0101358.Do D.N. et al. MicroRNA roles in signalling during lactation: an insight from differential expression, time course and pathway analyses of deep sequence data // Sci Rep. 2017. Vol. 7. P. 44605. https://doi.org/10.1038/srep44605.Do D.N. et al. MicroRNA roles in signalling during lactation: an insight from differential expression, time course and pathway analyses of deep sequence data // Sci Rep. 2017. Vol. 7. P. 44605. https://doi.org/10.1038/srep44605.Pan W. et al. MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1 // J. Immunol. 2010. Vol. 184. P. 6773 – 81. https://doi.org/10.4049/jimmunol.0904060.Pan W. et al. MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1 // J. Immunol. 2010. Vol. 184. P. 6773 – 81. https://doi.org/10.4049/jimmunol.0904060.Wagschal A. et al. Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis // Nat Med. 2015. Vol. 21. P. 1290 – 7. https://doi.org/10.1038/nm.3980.Wagschal A. et al. Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis // Nat Med. 2015. Vol. 21. P. 1290 – 7. https://doi.org/10.1038/nm.3980.Golan-Gerstl R. et al. Characterization and biological function of milk-derived microRNAs // Mol. Nutr. Food Res. 2017. https://doi.org/10.1002/mnfr.201700009.Golan-Gerstl R. et al. Characterization and biological function of milk-derived microRNAs // Mol. Nutr. Food Res. 2017. https://doi.org/10.1002/mnfr.201700009.Chen Z. et al. MicroRNA-145 regulates immune cytokines via targeting FSCN1 in Staphylococcus aureus- induced mastitis in dairy cows // Reprod. Domest. Anim. 2019. Vol. 54. № 6. P. 882 – 891. https://doi.org/10.1111/rda.13438.Chen Z. et al. MicroRNA-145 regulates immune cytokines via targeting FSCN1 in Staphylococcus aureus- induced mastitis in dairy cows // Reprod. Domest. Anim. 2019. Vol. 54. № 6. P. 882 – 891. https://doi.org/10.1111/rda.13438.Braud M. et al. Genome-wide microRNA binding site variation between extinct wild aurochs and modern cattle identifies candidate microRNA regulated domestication genes // Front Genet. 2017. Vol. 8. № 3. https://doi.org/10.3389/fgene.2017.00003.Braud M. et al. Genome-wide microRNA binding site variation between extinct wild aurochs and modern cattle identifies candidate microRNA regulated domestication genes // Front Genet. 2017. Vol. 8. № 3. https://doi.org/10.3389/fgene.2017.00003.Xiao C. et al. MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb // Cell. 2007. Vol. 131. P. 146 – 159. https://doi.org/10.1016/j.cell.2007.07.021.Xiao C. et al. MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb // Cell. 2007. Vol. 131. P. 146 – 159. https://doi.org/10.1016/j.cell.2007.07.021.Okuyama K. et al. MicroRNA-126–mediated control of cell fate in B-cell myeloid progenitors as a potential alternative to transcriptional factors // Proc. Natl. Acad. Sci. 2013. Vol. 110. P. 13410 – 13415. https://doi.org/10.1073/pnas.1220710110.Okuyama K. et al. MicroRNA-126–mediated control of cell fate in B-cell myeloid progenitors as a potential alternative to transcriptional factors // Proc. Natl. Acad. Sci. 2013. Vol. 110. P. 13410 – 13415. https://doi.org/10.1073/pnas.1220710110.Williams A.E. et al. Role of miRNA-146a in the regulation of the innate immune response and cancer // Biochem Soc Trans. 2008. Vol. 36. P. 1211 – 1215. https://doi.org/10.1042/BST0361211.Williams A.E. et al. Role of miRNA-146a in the regulation of the innate immune response and cancer // Biochem Soc Trans. 2008. Vol. 36. P. 1211 – 1215. https://doi.org/10.1042/BST0361211.Weber J.A. et al. The microRNA spectrum in 12 body fluids // Clin Chem. 2010. Vol. 56. P. 1733 – 1741. https://doi.org/10.1373/clinchem.2010.147405.Weber J.A. et al. The microRNA spectrum in 12 body fluids // Clin Chem. 2010. Vol. 56. P. 1733 – 1741. https://doi.org/10.1373/clinchem.2010.147405.Sun J. et al. MicroRNA expression profiles of bovine milk exosomes in response to Staphylococcus aureus infection // BMC Genomics. 2015. Vol. 16. № 16. P. 806. https://doi.org/10.1186/s12864-015-2044-9.Sun J. et al. MicroRNA expression profiles of bovine milk exosomes in response to Staphylococcus aureus infection // BMC Genomics. 2015. Vol. 16. № 16. P. 806. https://doi.org/10.1186/s12864-015-2044-9.Wu H. et al. miRNA Profiling of naïve, effector and memory CD8 T cells // PLoS ONE. 2007. Vol. 2: e1020. https://doi.org/10.1371/journal.pone.0001020.241.Wu H. et al. miRNA Profiling of naïve, effector and memory CD8 T cells // PLoS ONE. 2007. Vol. 2: e1020. https://doi.org/10.1371/journal.pone.0001020.241.Lai Y.C. et al. Inflammation-related microRNA expression level in the bovine milk is affected by mastitis // PLoS One. 2017. Vol. 12. P. 0177 – 182. https://doi.org/10.1371/journal.pone.0177182.Lai Y.C. et al. Inflammation-related microRNA expression level in the bovine milk is affected by mastitis // PLoS One. 2017. Vol. 12. P. 0177 – 182. https://doi.org/10.1371/journal.pone.0177182.Lai Y.C. et al. Bovine milk transcriptome analysis reveals microRNAs and RNU2 involved in mastitis // FEBS J. 2020. Vol. 287. № 9. P. 1899 – 1918. https://doi.org/10.1111/febs.15114.Lai Y.C. et al. Bovine milk transcriptome analysis reveals microRNAs and RNU2 involved in mastitis // FEBS J. 2020. Vol. 287. № 9. P. 1899 – 1918. https://doi.org/10.1111/febs.15114.Li R. et al. Comparative analysis of the miRNome of bovine milk fat, whey and cells // PLoS One. 2016. Vol. 11. e0154129. https://doi.org/10.1371/journal.pone.0154129.Li R. et al. Comparative analysis of the miRNome of bovine milk fat, whey and cells // PLoS One. 2016. Vol. 11. e0154129. https://doi.org/10.1371/journal.pone.0154129.Fang L. et al. Genome-Wide Transcriptional and Post-transcriptional Regulation of Innate Immune and Defense Responses of Bovine Mammary Gland to Staphylococcus aureus // Front Cell Infect Microbiol. 2016. Vol. 6. P. 193. https://doi.org/10.3389/fcimb.2016.00193.Fang L. et al. Genome-Wide Transcriptional and Post-transcriptional Regulation of Innate Immune and Defense Responses of Bovine Mammary Gland to Staphylococcus aureus // Front Cell Infect Microbiol. 2016. Vol. 6. P. 193. https://doi.org/10.3389/fcimb.2016.00193.Naeem A. et al. Bioinformatics analysis of microRNA and putative target genes in bovine mammary tissue infected with Streptococcus uberis // J. Dairy Sci. 2012. № 95. – P. 6397 – 408. https://doi.org/10.3168/jds.2011-5173.Naeem A. et al. Bioinformatics analysis of microRNA and putative target genes in bovine mammary tissue infected with Streptococcus uberis // J. Dairy Sci. 2012. № 95. – P. 6397 – 408. https://doi.org/10.3168/jds.2011-5173.Lawless N. et al. MicroRNA regulation of bovine monocyte inflammatory and metabolic networks in an in vivo infection model // G3 (Bethesda). 2014. Vol. 4. P. 957 – 71. https://doi.org/10.1534/g3.113.009936.Lawless N. et al. MicroRNA regulation of bovine monocyte inflammatory and metabolic networks in an in vivo infection model // G3 (Bethesda). 2014. Vol. 4. P. 957 – 71. https://doi.org/10.1534/g3.113.009936.Ngo S., Moloney S., Xiaoling L. Distinct MicroRNA signatures for mastitis measured in milk following natural exposure in dairy herds // Int. J. Anim. Sci. 2017. Vol. 1. P. 1001. https://doi.org/10.36876/ijas.1001.Ngo S., Moloney S., Xiaoling L. Distinct MicroRNA signatures for mastitis measured in milk following natural exposure in dairy herds // Int. J. Anim. Sci. 2017. Vol. 1. P. 1001. https://doi.org/10.36876/ijas.1001.Wang X. et al. Integrative Analysis of miRNA and mRNA Expression Profiles in Mammary Glands of Holstein Cows Artificially Infected with Staphylococcus Aureus // Pathogens. 2021. Vol. 10. P. 506.Wang X. et al. Integrative Analysis of miRNA and mRNA Expression Profiles in Mammary Glands of Holstein Cows Artificially Infected with Staphylococcus Aureus // Pathogens. 2021. Vol. 10. P. 506.Luoreng Z.M. et al. Comparison of microRNA Profiles between Bovine Mammary Glands Infected with Staphylococcus aureus and Escherichia coli // Int. J. Biol. Sci. 2018. Vol. 11. № 14 (1). P. 87 – 99. https://doi.org/10.7150/ijbs.22498.Luoreng Z.M. et al. Comparison of microRNA Profiles between Bovine Mammary Glands Infected with Staphylococcus aureus and Escherichia coli // Int. J. Biol. Sci. 2018. Vol. 11. № 14 (1). P. 87 – 99. https://doi.org/10.7150/ijbs.22498.Wang X.P. et al. Expression patterns of miR-146a and miR-146b in mastitis infected dairy cattle // Molecular and cellular probes. 2016. Vol. 30. № 5. P. 342 – 344. https://doi.org/10.1016/j.mcp.2016.08.004.Wang X.P. et al. Expression patterns of miR-146a and miR-146b in mastitis infected dairy cattle // Molecular and cellular probes. 2016. Vol. 30. № 5. P. 342 – 344. https://doi.org/10.1016/j.mcp.2016.08.004.Wang Z.C. et al. MiR-451 Inhibits synovial fibroblasts proliferation and inflammatory cytokines secretion in rheumatoid arthritis through mediating P38MAPK signaling pathway // Int. J. Clin. Exp. Pathol. 2015. Vol. 8. P. 14562.Wang Z.C. et al. MiR-451 Inhibits synovial fibroblasts proliferation and inflammatory cytokines secretion in rheumatoid arthritis through mediating P38MAPK signaling pathway // Int. J. Clin. Exp. Pathol. 2015. Vol. 8. P. 14562.Chen S. et al. Enhancer of Zeste Homolog 2 Is a Negative Regulator of Mitochondria-Mediated Innate Immune Responses // J. Immunol. 2013. Vol. 191. P. 2614 – 2623. https://doi.org/10.4049/jimmunol.1203143.Chen S. et al. Enhancer of Zeste Homolog 2 Is a Negative Regulator of Mitochondria-Mediated Innate Immune Responses // J. Immunol. 2013. Vol. 191. P. 2614 – 2623. https://doi.org/10.4049/jimmunol.1203143.Lawless N. et al. Next generation sequencing reveals the expression of a unique miRNA profile in response to a gram-positive bacterial infection // PLoS ONE. 2013. Vol. 8. e57543.Lawless N. et al. Next generation sequencing reveals the expression of a unique miRNA profile in response to a gram-positive bacterial infection // PLoS ONE. 2013. Vol. 8. e57543.Wang H. et al. MiR-145 regulates lipogenesis in goat mammary cells via targeting INSIG1 and epigenetic regulation of lipid-related genes // J. Cell. Physiol. 2017. Vol. 232. P. 1030–1040. https://doi.org/10.1002/jcp.25499.Wang H. et al. MiR-145 regulates lipogenesis in goat mammary cells via targeting INSIG1 and epigenetic regulation of lipid-related genes // J. Cell. Physiol. 2017. Vol. 232. P. 1030–1040. https://doi.org/10.1002/jcp.25499.

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