International Journal of Antibiotics Review Article

Prolonged Antibiotic Use and Reproductive Challenges in Dairy Cows: Implications for Ovarian, Uterine, and Overall Reproductive Health

  1. Md. Emran Hossain Department of Animal Science and Nutrition, Faculty of Veterinary Medicine, Chattogram Veterinary and Animal Sciences University

Abstract

The widespread use of antibiotics in dairy farming has raised concerns regarding its potential impact on reproductive performance. Prolonged antibiotic administration can disrupt endocrine regulation, alter ovarian function, impair uterine health, and compromise overall fertility in dairy cows. This review explores the multifaceted consequences of antibiotic exposure on reproductive physiology, highlighting its effects on hormonal balance, follicular dynamics, uterine microbiota, and embryo viability. Antibiotics may induce hormonal imbalances that interfere with estrous cyclicity, leading to anovulation, prolonged postpartum anestrus, and reduced conception rates. Ovarian dysfunction, characterized by impaired folliculogenesis and increased ovarian cyst formation, is another critical consequence. Additionally, prolonged antibiotic exposure alters the uterine microbiome, increasing susceptibility to endometritis and subclinical infections that hinder uterine involution and embryo implantation. The development of antimicrobial resistance in reproductive pathogens further complicates fertility management in dairy herds. Furthermore, antibiotic residues may persist in tissues, affecting fetal development and postnatal growth of offspring. Addressing these challenges requires an integrative approach, incorporating precision antibiotic use, alternative therapeutic strategies, and microbiome-targeted interventions to optimize reproductive efficiency. Future research should focus on understanding microbial-host interactions in reproductive tissues and developing sustainable solutions to minimize antibiotic-associated fertility decline in dairy cows.

Keywords

References (66)

  1. Gayathri SL, Bhakat M, Kumar A, Prasad S, Sharma N. Metritis in dairy cattle: Diagnostic challenges, economic impacts, and emerging insights. Curr J Appl Sci Technol. 2025;[Online]. Available from: http://openaccess.journals4promo.com/id/eprint/1753/
  2. Várhidi Z, Csikó G, Bajcsy ÁC, Jurkovich V. Uterine Disease in Dairy Cows: A Comprehensive Review Highlighting New Research Areas. Veterinary Sciences. 2024;11(2):66. doi:10.3390/vetsci11020066
  3. Dubuc J, Duffield TF, Leslie KE, Walton JS, LeBlanc SJ. Randomized clinical trial of antibiotic and prostaglandin treatments for uterine health and reproductive performance in dairy cows. Journal of Dairy Science. 2011;94(3):1325-1338. doi:10.3168/jds.2010-3757
  4. Refsdal AO. To treat or not to treat: a proper use of hormones and antibiotics. Animal Reproduction Science. 2000;60-61:109-119. doi:10.1016/s0378-4320(00)00094-4
  5. McDougall S. Effect of intrauterine antibiotic treatment on reproductive performance of dairy cows following periparturient disease. New Zealand Veterinary Journal. 2001;49(4):150-158. doi:10.1080/00480169.2001.36223
  6. Haimerl P, Heuwieser W. Invited review: Antibiotic treatment of metritis in dairy cows: A systematic approach. Journal of Dairy Science. 2014;97(11):6649-6661. doi:10.3168/jds.2014-8462
  7. Goshen T, Shpigel NY. Evaluation of intrauterine antibiotic treatment of clinical metritis and retained fetal membranes in dairy cows. Theriogenology. 2006;66(9):2210-2218. doi:10.1016/j.theriogenology.2006.07.017
  8. Trevisi E, Zecconi A, Cogrossi S, Razzuoli E, Grossi P, Amadori M. Strategies for reduced antibiotic usage in dairy cattle farms. Research in Veterinary Science. 2014;96(2):229-233. doi:10.1016/j.rvsc.2014.01.001
  9. Steffan J, Adriamanga S, Thibier M. Treatment of metritis with antibiotics or prostaglandin F2α and influence of ovarian cyclicity in dairy cows. Am J Vet Res. 1984;45(6):1090–4. Available from: https://avmajournals.avma.org/view/journals/ajvr/45/6/ajvr.1984.45.06.1090.xml
  10. Piccinno M, Rizzo A, Maselli MA, Derosa M, Sciorsci RL. Modulatory effect of three antibiotics on uterus bovine contractility in vitro and likely therapeutic approaches in reproduction. Theriogenology. 2014;82(9):1287-1295. doi:10.1016/j.theriogenology.2014.08.008
  11. Antibiotics. doi:10.3390/antibiotics
  12. A. Amin Y, Eldin Z. Mahmoud A, Sabry Aref M, El-Latif Shaker Seddek A, Younis W. Treatment of Endometritis Caused by Different Types of Bacteria by Cefoperazone Antibiotic and its Effect on the Days Open and Pregnancy Rate in Dairy Cows (Field Study). Journal of Animal Health and Production. 2021;10(3). doi:10.17582/journal.jahp/2022/10.3.311.319
  13. Drillich M. An update on uterine infections in dairy cattle. Veterinarski Zbornik. 2006 [Online]. Available from: http://www.vf.uni-lj.si/veterina/zbornik.htm
  14. Pinedo PJ, Velez J. Invited Review: Unique reproductive challenges for certified organic dairy herds. Applied Animal Science. 2019;35(4):416-425. doi:10.15232/aas.2019-01863
  15. Bretzlaff KN, Whitmore HL, Spahr SL, Ott RS. Incidence and treatments of postpartum reproductive problems in a dairy herd. Theriogenology. 1982;17(5):527-535. doi:10.1016/0093-691x(82)90178-9
  16. Azawi OI. Postpartum uterine infection in cattle. Animal Reproduction Science. 2008;105(3-4):187-208. doi:10.1016/j.anireprosci.2008.01.010
  17. Smadi MA, Mamache B, Ouennes H, Feriel F. Comparative study of treated and non-treated (auto-recovered) clinical endometritis effects on fertility parameters in dairy cows. Res Sq. 2024;[Online]. Available from: https://www.researchsquare.com/article/rs-4408948/latest
  18. Appiah M, Wang J, Lu W. Microflora in the Reproductive Tract of Cattle: A Review. Agriculture. 2020;10(6):232. doi:10.3390/agriculture10060232
  19. M. A. Lammoglia. Effect of hormonal and antibiotic treatment of Holstein cows with uterine discharges at 25 days in milk on reproductive performance in Mexican Plateau. Scientific Research and Essays. 2011;6(32). doi:10.5897/sre11.644
  20. Vlietstra RJ. The impact of postpartum hormonal intervention on uterine health and fertility of dairy cows [dissertation]. Guelph (ON): University of Guelph; 2019. Available from: https://search.proquest.com/openview/825843834927cc137b378e788ab12845
  21. Muratbayev DM, Tokayev ZK, Akhmetzhanov ON, Ygieva AS, Mukhamadieva NN. Ovarian Disorders Treatment in Dairy Cows with Infertility. Advances in Animal and Veterinary Sciences. 2018;6(10). doi:10.17582/journal.aavs/2018/6.10.436.442
  22. Hashem NM, Gonzalez-Bulnes A. Nanotechnology and Reproductive Management of Farm Animals: Challenges and Advances. Animals. 2021;11(7):1932. doi:10.3390/ani11071932
  23. Amin Y, Omran G, Fouad S, Fawy M, Ibrahim R, Khalifa F, et al. Abortion associated with postpartum opportunistic bacterial invasion reduces fertility and induces disturbances of reproductive hormones, hematological profile, and oxidant/antioxidant profiles in dairy cows. Journal of Advanced Veterinary and Animal Research. 2024:1. doi:10.5455/javar.2023.j721
  24. Tucho TT. Review on retention of placenta in dairy cows and its economic and reproductive impacts. Int J Sci Technol Res. 2017;3(6):15–22. Available from: http://www.iiste.org
  25. Smith BI. Therapeutic and management options for postpartum metritis in dairy cattle. Vet Learn Syst. 2005;24(10):S92–8. Available from: http://assets.prod.vetlearn.com.s3.amazonaws. com/mmah/9d/5d4977d4ed4e52b13e1aa2fb19a048/filePV_24_10_S92.pdf
  26. Manimaran A, Kumaresan A, Jeyakumar S, Rajendran D. Therapeutic Management of Postpartum Uterine Infections in Bovines. Current Concepts in Bovine Reproduction. 2022:197-222. doi:10.1007/978-981-19-0116-4_11
  27. Elmetwally MA. Uterine Involution and Ovarian Activity in Postpartum Holstein Dairy Cows. A Review. Journal of Veterinary Healthcare. 2018;1(4):29-40. doi:10.14302/issn.2575-1212.jvhc-18-2447
  28. Dahiya S, Kumari S, Rani P, Onteru SK, Singh D. Postpartum uterine infection & ovarian dysfunction. Indian Journal of Medical Research. 2018;148(Suppl1):S64-S70. doi:10.4103/ijmr.ijmr_961_18
  29. Huszenicza G, Fodor M, Gacs M, Kulcsar M, Dohmen M, Vamos M, et al. Uterine Bacteriology, Resumption of Cyclic Ovarian Activity and Fertility in Postpartum Cows kept in Large‐Scale Dairy Herds. Reproduction in Domestic Animals. 1999;34(3-4):237-245. doi:10.1111/j.1439-0531.1999.tb01246.x
  30. Pancarci ŞM, Gürbulak K, Oral H, Karapehlivan M, Tunca R, Çolak A. Effect of immunomodulatory treatment with levamisole on uterine inflammation and involution, serum sialic acid levels and ovarian function in cows. Kafkas Univ Vet Fak Derg. 2009;15(6):935–42. Available from: https://vetdergikafkas.org/pdf.php?id=428
  31. Jeengar K, Chaudhary V, Kumar A, Raiya S, Gaur M, Purohit GN. Ovarian cysts in dairy cows: Old and new concepts for definition, diagnosis and therapy. Anim Reprod. 2014;11(2):63–73. Available from: https://www.animal-reproduction.org/article/5b5a6042f7783717068b4668/pdf
  32. Peter A. An Update on Cystic Ovarian Degeneration in Cattle. Reproduction in Domestic Animals. 2004;39(1):1-7. doi:10.1046/j.0936-6768.2003.00466.x
  33. Roche JR, Burke CR, Crookenden MA, Heiser A, Loor JL, Meier S, et al. Fertility and the transition dairy cow. Reproduction, Fertility and Development. 2017;30(1):85-100. doi:10.1071/rd17412
  34. Sheldon IM, Dobson H. Postpartum uterine health in cattle. Animal Reproduction Science. 2004;82-83:295-306. doi:10.1016/j.anireprosci.2004.04.006
  35. Sheldon IM, Cronin J, Goetze L, Donofrio G, Schuberth HJ. Defining Postpartum Uterine Disease and the Mechanisms of Infection and Immunity in the Female Reproductive Tract in Cattle1. Biology of Reproduction. 2009;81(6):1025-1032. doi:10.1095/biolreprod.109.077370
  36. Sheldon IM, Williams EJ, Miller ANA, Nash DM, Herath S. Uterine diseases in cattle after parturition. The Veterinary Journal. 2008;176(1):115-121. doi:10.1016/j.tvjl.2007.12.031
  37. Bromfield JJ, Santos JEP, Block J, Williams RS, Sheldon IM. Uterine infection: Linking infection and innate immunity with infertility in the high-producing dairy cow. J Anim Sci. 2015;93(5):2021–33. doi:10.2527/jas.2014-8496.
  38. Sheldon IM. The postpartum uterus. Veterinary Clinics of North America: Food Animal Practice. 2004;20(3):569-591. doi:10.1016/j.cvfa.2004.06.008
  39. Lewis GS. Uterine Health and Disorders. Journal of Dairy Science. 1997;80(5):984-994. doi:10.3168/jds.s0022-0302(97)76024-7
  40. Galvão KN. Uterine diseases in dairy cows: Understanding the causes and seeking solutions. Anim Reprod. 2013;10(3):228–38. Available from: https://animal-reproduction.org/journal/animreprod /article/5b5a604af7783717068b4696
  41. LeBlanc SJ. Postpartum uterine disease and dairy herd reproductive performance: A review. The Veterinary Journal. 2008;176(1):102-114. doi:10.1016/j.tvjl.2007.12.019
  42. Çömlekcioğlu U, Jezierska S, Opsomer G, Pascottini OB. Uterine microbial ecology and disease in cattle: A review. Theriogenology. 2024;213:66-78. doi:10.1016/j.theriogenology.2023.09.016
  43. Gilbert RO. The effects of endometritis on the establishment of pregnancy in cattle. Reproduction, Fertility and Development. 2011;24(1):252-257. doi:10.1071/rd11915
  44. Adnane M, Whiston R, Tasara T, Bleul U, Chapwanya A. Harnessing Vaginal Probiotics for Enhanced Management of Uterine Disease and Reproductive Performance in Dairy Cows: A Conceptual Review. Animals. 2024;14(7):1073. doi:10.3390/ani14071073
  45. Gilbert RO. Symposium review: Mechanisms of disruption of fertility by infectious diseases of the reproductive tract. Journal of Dairy Science. 2019;102(4):3754-3765. doi:10.3168/jds.2018-15602
  46. Abdisa T. Review on the Reproductive Health Problem of Dairy Cattle. Journal of Dairy & Veterinary Sciences. 2018;5(1). doi:10.19080/jdvs.2018.05.555655
  47. LeBlanc SJ. Review: Postpartum reproductive disease and fertility in dairy cows. animal. 2023;17:100781. doi:10.1016/j.animal.2023.100781
  48. Ibrahim N. A review on reproductive health problems in dairy cows in Ethiopia. J Vet Med Anim Health. 2017;9(4):56–65. Available from: https://www.researchgate.net/profile/Nuraddis-Ibrahim/publication/322577249
  49. Ribeiro ES, Carvalho MR. Impact and mechanisms of inflammatory diseases on embryonic development and fertility in cattle. Animal Reproduction. 2017;14(3):589-600. doi:10.21451/1984-3143-ar1002
  50. Fricke PM, Shaver RD. Managing reproductive disorders in dairy cows. Univ Wisconsin Ext Publ. 2001. Available from: https://www.researchgate.net/profile/Paul-Fricke/publication/251762927
  51. Wang N, Chen L, Yi K, Zhang B, Li C, Zhou X. The effects of microbiota on reproductive health: A review. Critical Reviews in Food Science and Nutrition. 2022;64(6):1486-1507. doi:10.1080/10408398.2022.2117784
  52. Kumaresan A, Praveen KS, Manimaran A, Srivastava AK. Uterine Infection in Bovines: An Update. Current Concepts in Bovine Reproduction. 2022:169-195. doi:10.1007/978-981-19-0116-4_10
  53. Reproduction in Cattle. 2004. doi:10.1002/9780470751091
  54. Santos JEP, Ribeiro ES. Impact of animal health on reproduction of dairy cows. Anim Reprod. 2014;11(3):254–69. Available from: https://www.animal-reproduction.org/article/5b5a604 0f7783717068b465c
  55. Thatcher W, Santos J, Silvestre F, Kim I, Staples C. Perspective on Physiological/Endocrine and Nutritional Factors Influencing Fertility in Post‐partum Dairy Cows. Reproduction in Domestic Animals. 2010;45(s3):2-14. doi:10.1111/j.1439-0531.2010.01664.x
  56. Sheldon IM, Wathes DC, Dobson H. The management of bovine reproduction in elite herds. The Veterinary Journal. 2006;171(1):70-78. doi:10.1016/j.tvjl.2004.06.008
  57. Uçar Ö, Ağırbaş D. A Holistic Approach to the Effects of Intrauterine Antimicrobial Therapy on Pregnancy Rate after Artificial Insemination in Dairy Cows. Black Sea Journal of Health Science. 2022;5(3):591-596. doi:10.19127/bshealthscience.1089471
  58. Gupta D, Sarkar A, Pal Y, Suthar V, Chawade A, Kushwaha SK. Bovine reproductive tract and microbiome dynamics: current knowledge, challenges, and its potential to enhance fertility in dairy cows. Frontiers in Microbiomes. 2024;3. doi:10.3389/frmbi.2024.1473076
  59. Adnane M, Chapwanya A. Microbial Gatekeepers of Fertility in the Female Reproductive Microbiome of Cattle. International Journal of Molecular Sciences. 2024;25(20):10923. doi:10.3390/ijms252010923
  60. Gonzalez Moreno C, Fontana C, Cocconcelli PS, Callegari ML, Otero MC. Vaginal microbial communities from synchronized heifers and cows with reproductive disorders. Journal of Applied Microbiology. 2016;121(5):1232-1241. doi:10.1111/jam.13239
  61. Gholiof M, Adamson-De Luca E, Wessels JM. The female reproductive tract microbiotas, inflammation, and gynecological conditions. Frontiers in Reproductive Health. 2022;4. doi:10.3389/frph.2022.963752
  62. Becker AAMJ, Munden S, McCabe E, Hurley D, Fanning S, Chapwanya A, et al. The Endometrial Microbiota—16S rRNA Gene Sequence Signatures in Healthy, Pregnant and Endometritis Dairy Cows. Veterinary Sciences. 2023;10(3):215. doi:10.3390/vetsci10030215
  63. Singh M, Sharma A, Sharma A, Kumar P. Repeat breeding and its treatment in dairy cattle of Himachal Pradesh, India: A review. Int J Agric Res. 2017;12(2):45–53. Available from: https://acspublisher.com/journals/index.php/ijar/article/view/3712
  64. Kashoma I, Ngou AA. Retained fetal membrane in Tanzanian dairy cows: Economic impacts and subsequent reproductive performance. ResGate Preprint. 2025. Available from: https://www.researchgate.net/profile/Athanas-Ngou/publication/388617005
  65. Akhmadov VT, Bersanova KI. Morphological changes in the genitals of cows with hypotension with uterine atony. AIP Conference Proceedings. 2021;2442:030007. doi:10.1063/5.0076483
  66. Jeremejeva J, Orro T, Waldmann A, Kask K. Treatment of dairy cows with PGF2α or NSAID, in combination with antibiotics, in cases of postpartum uterine inflammation. Acta Veterinaria Scandinavica. 2012;54(1). doi:10.1186/1751-0147-54-45