Ketosis and its role in Bos taurus reproductive impairment

Cover Page

Cite item


The analysis of relevant and significant scientific research on the physiological and biochemical aspects of ketosis, and the main mechanisms of influence on reproductive function in this metabolic pathology is presented. Strengthening breeding potential and creating conditions for its implementation through modern feeding and maintenance technologies led to the spread of diseases of non-communicable etiology, including ketosis diseases. Ketotic diseases cause various disorders in carbohydrate-lipid, protein, water-electrolyte and vitamin-mineral metabolism. The monitoring of studies on the biological role of ketosis showed its effect on animal fertility, quality of female gametes and fetal development. When considering ketosis, it is important to understand precisely the mechanisms of influence, since many methods for diagnosing and combating ketosis diseases are based on their knowledge. The key mechanisms of ketone bodies formation, the reasons for increase in their concentration were considered. It is of great practical importance for development of diagnostic tests that make it possible to determine the direction of disturbances in energy and plastic processes. Based on the data presented in the studies, conclusions were drawn about the role of β-hydroxybutyric acid as a direct factor in reducing the reproductive function of Bos taurus .

About the authors

Gennady V. Shiryaev

L. K. Ernst Federal Science Center for Animal Husbandry

Author for correspondence.

PhD (Agr. Sci.), Senior Researcher, Department of Reproduction of Farm Animals

55a, Moscow highway, Pushkin, St. Petersburg, 196601, Russian Federation

Tatyana I. Stanislavovich

L. K. Ernst Federal Science Center for Animal Husbandry


PhD (Agr. Sci.), Leading Researcher, Laboratory of Development Biology

55a, Moscow highway, Pushkin, St. Petersburg, 196601, Russian Federation

Vladimir P. Politov

L. K. Ernst Federal Science Center for Animal Husbandry



55a, Moscow highway, Pushkin, St. Petersburg, 196601, Russian Federation


  1. Mellado M, Dávila А, Gaytan L, Macias-Cruz U, Avendano-Reyes L, et al. Risk factors for clinical ketosis and association with milk production and reproduction variables in dairy cows in a hot environment. Tropical Animal Health and Production. 2018; 7(50):1611—1616. doi: 10.1007/s11250-018-1602-у
  2. Mostert PF, Bokkers EAM, Van Middelaar CE, Hogeveen H, de Boer IJM. Тhe economic impact of subclinical ketosis in dairy cattle using a dynamic stochastic simulation model. Animal. 2018; 12(1):145-154. doi: 10.1017/S1751731117001306
  3. Shiryaev GV, Nikitin GS. Evaluation of the use of feed additives in subclinical ketosis in highly productive cows. Issues of Legal Regulation in Veterinary Medicine. 2020; (2):45—50. doi: 10.17238/issn20726023.2020.2.45
  4. Duffield TF, Lissemore KD, McBride BW, Leslie KE. Impact of hyperketonemia in early lactation dairy cows on health and production. Journal of Dairy Science. 2009; 92(2):571—580. doi: 10.3168/jds.2008-1507
  5. Diskin MG, Murphy JJ, Sreenan JM. Embryo survival in dairy cows managed under pastoral conditions. Animal Reproduction Science. 2006; (96):3-4:297—311. doi: 10.1016/j.anireprosci.2006.08.008
  6. Suthar VS, Canelas-Raposo J, Deniz A, Heuwieser W. Prevalence of subclinical ketosis and relationships with postpartum diseases in European dairy cows. Journal of Dairy Science. 2013; 96(5):2925—2938. doi: 10.3168/jds.2012-6035
  7. Rutherford AJ, Oikonomou G, Smith RF. The effect of subclinical ketosis on activity at estrus and reproductive performance in dairy cattle. Journal of Dairy Science. 2016; 99(6):4808—4815. doi: 10.3168/ jds.2015-10154
  8. Walsh RB, Walton JS, Kelton DF, Le Blanc SJ, Leslie KE, et al. Effect of subclinical ketosis in early lactation on reproductive performance of postpartum dairy cows. Journal of Dairy Science. 2007; 90(6): 2788—2796. doi: 10.3168/jds.2006-560
  9. Antanaitis R, Juozaitienė V, Malašauskienė D, Televičius M, Urbutis M. Biomarkers from automatic milking system as an indicator of subclinical acidosis and subclinical ketosis in fresh dairy cows. Polish Journal of Veterinary Sciences. 2019; 22(4):685—693. doi: 10.24425/pjvs.2019.129981
  10. Elenshleger AA, Trebukhov AV, Kazakova OG. Some biochemical blood indices in cows with subclinical ketosis. Bulletin of Altai State Agricultural University. 2014; (10):96—99. (In Russ).
  11. Danchenko EO. Biochemical markers of alcoholic ketoacidosis. Forensic Examination of Belarus. 2017; (1):37—45. (In Russ).
  12. Voinova AA., Kovalev S.P., Trushkin V.A., Nikitin G.S. Change of pigment metabolism indicators in treatment of cows affected by chronic hepatosis. International Bulletin of Veterinary Medicine. 2018; (1):114—118. (In Russ).
  13. Zilberter YI, Zilberter TM. Power metabolism: from neurons and glia to the whole brain; norm, pathology and correction. Progress in Physiological Science. 2012; 43(2):37—53. (In Russ).
  14. Bogolyubova NV, Romanov VN, Rykov RA. Features of metabolic processes in the body of cows with the use of additional nutrition in the diets. Genetics and breeding of animals. 2019; (4):92—97. (In Russ). doi: 10.31043/2410-2733-2019-3-3-10
  15. Taganovich AD, Oletskii EI, Konevalova NY, Lelevich VV. Biologicheskaya khimiya [Biological chemistry]. Minsk: Vysheishaya shchkola Publ.; 2013. (In Russ).
  16. Cardo L. Solving the problem of negative energy balance. Effektivnoe zhivotnovodstvo. 2015; (7):30—31. (In Russ).
  17. Maslovskaya AA. Mechanism of ketosis in diabetes mellitus and starvation. Journal of the Grodno State Medical University. 2012; 3:8—10. (In Russ).
  18. McCarthy MM, Mann S, Nydam DV, Overton TR, McArt JAA. Short communication: Concentrations of nonesterified fatty acids and β-hydroxybutyrate in dairy cows are not well correlated during the transition period. Journal of Dairy Science. 2015; 98(9):6284—6290. doi: 10.3168/jds.2015-9446
  19. Butler WR. Energy balance relationships with follicular development, ovulation and fertility in postpartum dairy cows. Livestock Production Science. 2003; 83(2-3):211—218. doi: 10.1016/S0301-6226(03)00112-X
  20. Zarrin M, De Matteis L, Vernay MCMB, Wellnitz O, van Dorland H.A, et al. Long-term elevation of β-hydroxybutyrate in dairy cows through infusion: Effects on feed intake, milk production, and metabolism. Journal of Dairy Science. 2013; 96(5):2960—2972. doi: 10.3168/jds.2012-6224
  21. Metz SHM, van den Bergh SG. Regulation of fat mobilization in adipose tissue of dairy cows in the period around parturition. Netherlands Journal of Agricultural Science. 1977; 25(3):198—211. doi: 10.18174/ njas.v25i3.17132
  22. Van der Drift SGA, Everts RR, Houweling M, van Leengoed LAMG, Stegeman JA, et al. Effects of β-hydroxybutyrate and isoproterenol on lipolysis in isolated adipocytes from periparturient dairy cows and cows with clinical ketosis. Research in Veterinary Science. 2013; 94(3):433—439. doi: 10.1016/j.rvsc.2012.11.009
  23. Lemor A, Hosseini A, Sauerwein H, Mielenz M. Transition period-related changes in the abundance of the mRNAs of adiponectin and its receptors, of visfatin, and of fatty acid binding receptors in adipose tissue of high-yielding dairy cows. Domestic Animal Endocrinology. 2009; 37(1):37—44. doi: 10.1016/j. domaniend.2009.01.004
  24. Yamdagni S, Schultz LH. Fatty acid composition of blood plasma lipids of normal and ketotic cows. Journal of Dairy Science. 1970; 53(8):1046—1050. doi: 10.3168/jds.S0022-0302(70)86343-3
  25. Brumby PE, Anderson M, Tuckley B, Storry JE, Hibbit KG. Lipid Metabolism in the Cow during Starvation-Induced Ketosis. Biochemical Journal. 1975; 146(3):609—615. doi: 10.1042/bj1460609
  26. Fiore ЕТ, Tessari R, Morgante М, Gianesella M, Badon T, et al. Identification of Plasma Fatty Acids in Four Lipid Classes to Understand Energy Metabolism at Different Levels of Ketonemia in Dairy Cows Using Thin Layer Chromatography and Gas Chromatographic Techniques (TLC-GC). Animals. 2020; 10(4):571. doi: 10.3390/ani10040571
  27. Aardema H, van Tol HTA, Wubbolts RW, Brouwers JFHM, Gadella BM, et al. Stearoyl-CoA desaturase activity in bovine cumulus cells protects the oocyte against saturated fatty acid stress. Biology of Reproduction. 2017; 96(5):982—992. doi: 10.1095/biolreprod.116.146159
  28. Du X, Zhu Y, Peng Z, Cui Y, Zhang Q, et al. High concentrations of fatty acids and β-hydroxybutyrate impair the growth hormone-mediated hepatic JAK2-STAT5 pathway in clinically ketotic cows. Journal of Dairy Science. 2018; 101(4):3476—3487. doi: 10.3168/jds.2017-13234
  29. Silva JRV, Figueiredo JR, van den Hurk R. Involvement of growth hormone (GH) and insulin-like growth factor (IGF) system in ovarian folliculogenesis. Theriogenology. 2009; 71(8): 1193—1208. doi: 10.1016/j. theriogenology.2008.12.015
  30. Heidari M, Kafi M, Mirzaei A, Asaadi A, Mokhtari A. Effects of follicular fluid of preovulatory follicles of repeat breeder dairy cows with subclinical endometritis on oocyte developmental competence. Animal Reproduction Science. 2019; 205:62—69. doi: 10.1016/j.anireprosci.2019.04.004
  31. Nasioudis D, Minis E, Irani M, Kreines M, Witkin SS, et al. Insulin-like growth factor-1 and soluble FMS-like tyrosine kinase-1 prospectively predict cancelled IVF cycles. Journal of Assisted Reproduction and Genetics. 2019; 36(12):2485—2491. doi: 10.1007/s10815-019-01618-3
  32. Tresnitskiy SN, Avdeenko VS, Pimenov NV. Metabolic stress in dry cows and heifers during the development of subclinical ketosis. Veterinary, Zootechnics and Biotechnology. 2017; (12): 6—13. (In Russ).
  33. Avdeenko VS, Kalyuzhny II, Tresnitskiy SN. Metabolic stress in dry cows and nets in development of subclinical ketosis. Veterinary Medicine. 2019; (2):36—41. (In Russ). doi: 10.30896/0042-4846.2019.22.2.36-41
  34. Tresnitsky SN. Teoreticheskoe obosnovanie i prakticheskoe primenenie innovatsionnykh tekhnologii v diagnostike, terapii i profilaktike eklampticheskogo sindroma u korov [Theoretical substantiation and practical application of innovative technologies in the diagnosis, therapy and prevention of eclamptic syndrome in cows] [Dissertation] Saratov; 2018 (In Russ).
  35. Nakagawa H, Katoh N. Reduced activity of lecithin: Cholesterol acyltransferase in the serum of cows with ketosis and left displacement of the abomasum. Veterinary Research Communications. 1998; 22(8):517—524. doi: 10.1023/a:1006189603071
  36. Mc Fadden JW. Review: Lipid biology in the periparturient dairy cow: contemporary perspectives. Animal. 2020; 14(S1): s165—s175. doi: 10.1017/S1751731119003185
  37. Leroy J, Vanholder T, Opsomer G, Van Soom A, Kruif A. The In Vitro Development of Bovine Oocytes after Maturation in Glucose and beta-Hydroxybutyrate Concentrations Associated with Negative Energy Balance in Dairy Cows. Reproduction in Domestic Animals. 2006; 41(2):119—123. doi: 10.1111/j.1439-0531.2006.00650.x
  38. Lukashik GV. Morphological and cytochemical changes of blood cells at highly productive cows at metabolism infringement. Transactions of Taurida Agricultural Science. 2014; (160):130—135. (In Russ).
  39. Hoeben D, Heyneman R, Burvenich C. Elevated levels of β-hydroxybutyric acid in periparturient cows and in vitro effect on respiratory burst activity of bovine neutrophils. Veterinary Immunology and Immunopathology. 1997; 58(2):165—170. doi: 10.1016/S0165-2427(97)00031-7
  40. Zdzisińska B, Filar J, Paduch R, Kaczor J, Lokaj I, et al. The influence of ketone bodies and glucose on interferon, tumor necrosis factor production and NO release in bovine aorta endothelial cells. Veterinary Immunology and Immunopathology. 2000; 74(3-4):237—247. doi: 10.1016/S0165-2427(00)00175-6
  41. Yarovan NI, Novikova IA. Oxidative stress in highly productive cows with subclinical ketosis in industrial conditions. Bulletin of agrarian science. 2012; (5):146—148.
  42. Shi X, Li X, Li D, Li Y, Song Y, et al. β-Hydroxybutyrate activates the NF-κB signaling pathway to promote the expression of pro-inflammatory factors in calf hepatocytes. Cellular Physiology and Biochemistry. 2014; 33(4):920—932.
  43. Song Y, Li N, Gu J, Fu S, Peng Z, et al. β-Hydroxybutyrate induces bovine hepatocyte apoptosis via an ROS-p38 signaling pathway. Journal of Dairy Science. 2016; 99(11):9184—9198. doi: 10.3168/jds.2016-11219
  44. Kovalyov SP, Shcherbakov GG, Radnatarov VD, Kiselenko PS, Trushkin VA, et al. Vitamin exchange in cows suffering from ketosis. Issues of Legal regulation in veterinary medicine. 2018; (2):140—142.
  45. Gupta RK, Miller KP, Babus JK, Flaws JA. Methoxychlor inhibits growth and induces atresia of antral follicles through an oxidative stress pathway. Toxicological Sciences. 2006; 93(2):382-389. doi: 1093/toxsci/kfl052
  46. Devine PJ, Perreault SD, Luderer U. Roles of reactive oxygen species and antioxidants in ovarian toxicity. Biology of Reproduction. 2012; 86(2): 1—10. doi: 10.1095/biolreprod.111.095224

Copyright (c) 2020 Shiryaev G.V., Stanislavovich T.I., Politov V.P.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies