Veterinary Research Forum
Vet Res Forum

Plasma microRNAs as non-invasive biomarkers in bovine endometritis caused by Gram-negative and Gram-positive bacteria

Document Type : Original Article

Authors

Arman Shokri 1
Reza Asadpour 1
Razi Jafai-joozani 1
Esmaeil Babaei 2
Abolfazl Hajibemani 1
Gholamreza Hamidian 3

1 Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran

2 Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

3 Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran

https://doi.org/10.30466/vrf.2022.555375.3505
Abstract
The purpose was to identify differentially expressed plasma microRNAs (miRNAs) in cows with clinical and subclinical endometritis. In this study clinical endometritis (CE; n = 23) based on vaginal discharge score (VDS), subclinical endometritis (SCE; n = 17) based on VDS (0), and endometrial cytology (the presence of 8.00% polymorphonuclear neutrophils (PMN) on days 21-31 and 5.00% on days 41-51 days in milk (DIM) and healthy cows (n = 21) based on vaginal discharge score (0), and endometrial cytology (< 5.00% PMN on days 21 - 31 and < 5.00% on days 41 - 51 DIM) were selected. The results showed that the expression level of miR-146a was significantly higher in the CE (19.17-fold), and SCE (6.22-fold) groups than those of healthy cows. The relative transcript abundance of miR-223 was considerably down-regulated in the CE (0.26-fold) and SCE (0.06-fold) compared to the healthy cows. The expression levels of miR-146a and miR-223 were significantly higher in the CE group which could be caused by Gram-negative bacterial infection. Our results showed that the expression level of plasma miRNAs postpartum could be used as a reliable marker to distinguish between SCE, CE and healthy cows.

Keywords

Bacteria
Dairy cattle
Endometritis
microRNAs
Plasma
Subjects
  1. Sheldon IM, Williams EJ, Miller AN, et al. Uterine diseases in cattle after parturition. Vet J 2008; 176(1): 115-121.
  2. Van Schyndel SJ, Bogado Pascottini O, LeBlanc SJ. Comparison of cow-side diagnostic techniques for subclinical endometritis in dairy cows. Theriogenology 2018; 120: 117-122.
  3. Opsomer G, Gröhn YT, Hertl J, et al. Risk factors for post partum ovarian dysfunction in high producing dairy cows in Belgium: a field study. Theriogenology 2000; 53(4): 841-857.
  4. LeBlanc SJ. Postpartum uterine disease and dairy herd reproductive performance: a review. Vet J 2008; 176(1): 102-114.
  5. Gilbert RO, Shin ST, Guard CL, et al. Prevalence of endometritis and its effects on reproductive performance of dairy cows. Theriogenology 2005; 64(9): 1879-1888.
  6. Van Schyndel SJ, Carrier J, Bogado Pascottini O, et al. The effect of pegbovigrastim on circulating neutrophil count in dairy cattle: A randomized controlled trial. PloS One 2018; 13(6): e0198701. doi: 10.1371/journal. pone.0198701.
  7. Moraes JGN, Silva PRB, Mendonça LGD, et al. Risk factors for purulent vaginal discharge and its association with reproductive performance of lactating Jersey cows. J Dairy Sci 2021; 104(12): 12816-12829.
  8. Potter TJ, Guitian J, Fishwick J, et al. Risk factors for clinical endometritis in postpartum dairy cattle. Theriogenology 2010; 74(1): 127-134.
  9. Dohmen MJ, Joop K, Sturk A, et al. Relationship between intra-uterine bacterial contamination, endotoxin levels and the development of endometritis in postpartum cows with dystocia or retained placenta. Theriogenology 2000; 54(7): 1019-1032.
  10. Williams EJ, Fischer DP, Noakes DE, et al. The relationship between uterine pathogen growth density and ovarian function in the postpartum dairy cow. Theriogenology 2007; 68(4): 549-559.
  11. Turner ML, Cronin JG, Healey GD, et al. Epithelial and stromal cells of bovine endometrium have roles in innate immunity and initiate inflammatory responses to bacterial lipopeptides in vitro via Toll-like receptors TLR2, TLR1, and TLR6. Endocrinology 2014; 155(4): 1453-1465.
  12. LeBlanc SJ. Interactions of metabolism, inflammation, and reproductive tract health in the postpartum period in dairy cattle. Reprod Domest Anim 2012; 47(Suppl 5): 18-30.
  13. Sheldon IM, Lewis GS, LeBlanc S, et al. Defining postpartum uterine disease in cattle. Theriogenology 2006; 65(8): 1516-1530.
  14. Sheldon IM, Price SB, Cronin J, et al. Mechanisms of infertility associated with clinical and subclinical endometritis in high producing dairy cattle. Reprod Domest Anim 2009; 44(Suppl 3): 1-9.
  15. Kasimanickam R, Duffield TF, Foster RA, et al. Endometrial cytology and ultrasonography for the detection of subclinical endometritis in postpartum dairy cows. Theriogenology 2004; 62(1-2): 9-23.
  16. McDougall S, Aberdein D, Bates A, et al. Prevalence of endometritis diagnosed by vaginal discharge scoring or uterine cytology in dairy cows and herds. J Dairy Sci 2020; 103(7): 6511-6521.
  17. Pleticha S, Heuwieser W. Definition and diagnosis of chronic endometritis in cattle: a review [German]. Dtsch Tierarztl Wochenschr 2009; 116(5): 164-172.
  18. Barlund CS, Carruthers TD, Waldner CL, et al. A comparison of diagnostic techniques for postpartum endometritis in dairy cattle. Theriogenology 2008; 69(6): 714-723.
  19. Neudecker V, Haneklaus M, Jensen O, et al. Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome. J Exp Med 2017; 214(6): 1737-1752.
  20. Tesfaye D, Salilew-Wondim D, Gebremedhn S, et al. Potential role of microRNAs in mammalian female fertility. Reprod Fertil Dev 2016; 29(1): 8-23.
  21. Jiang K, Yang J, Yang C, et al. miR‐148a suppresses inflammation in lipopolysaccharide‐induced endometritis. J Cell Mol Med 2020; 24(1): 405-417.
  22. Salilew-Wondim D, Ibrahim S, Gebremedhn S, et al. Clinical and subclinical endometritis induced alterations in bovine endometrial transcriptome and miRNome profile. BMC Genomics 2016; 17: 218. doi: 10.1186/s12864-016-2513-9.
  23. Oladejo AO, Li Y, Wu X, et al. MicroRNAome: potential and veritable immunomolecular therapeutic and diagnostic baseline for lingering bovine endometritis. Front Vet Sci 2020; 7: 614054. doi: 10.3389/fvets. 2020.614054.
  24. Ibrahim S, Salilew-Wondim D, Rings F, et al. Expression pattern of inflammatory response genes and their regulatory microRNAs in bovine oviductal cells in response to lipopolysaccharide: implication for early embryonic development. PloS One 2015; 10(3): e0119388. doi: 10.1371/journal.pone.0119388.
  25. Liu Y, Shi W, Zhou E, et al. Dynamic changes in inflammatory cytokines in pigs infected with highly pathogenic porcine reproductive and respiratory syndrome virus. Clin Vaccine Immunol 2010; 17(9): 1439-1445.
  26. Bhaumik D, Scott GK, Schokrpur S, et al. Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene 2008; 27(42): 5643-5647.
  27. Yin P, Zhang Z, Li J, et al. Ferulic acid inhibits bovine endometrial epithelial cells against LPS-induced inflammation via suppressing NK-κB and MAPK pathway. Res Vet Sci 2019; 126: 164-169.
  28. Hailemariam D, Ibrahim S, Hoelker M, et al. MicroRNA-regulated molecular mechanism underlying bovine subclinical endometritis. Reprod Fertil Dev 2014; 26(6): 898-913.
  29. Zhao G, Jiang K, Yang Y, et al. The potential therapeutic role of miR-223 in bovine endometritis by targeting the NLRP3 inflammasome. Front Immunol 2018; 9: 1916. doi: 10.3389/fimmu.2018.01916.
  30. Sheldon IM, Noakes DE, Rycroft AN, et al. The effect of intrauterine administration of estradiol on postpartum uterine involution in cattle. Theriogenology 2003; 59(5-6): 1357-1371.
  31. Okawa H, Fujikura A, Wijayagunawardane MMP, et al. Effect of diagnosis and treatment of clinical endometritis based on vaginal discharge score grading system in postpartum Holstein cows. J Vet Med Sci 2017; 79(9): 1545-1551.
  32. Markey B, Leonard F, Archambault M, et al. Clinical veterinary microbiology e-book. 2nd London, UK: Mosby Ltd. 2013; 161-176.
  33. Ioannidis J, Donadeu FX. Circulating miRNA signatures of early pregnancy in cattle. BMC Genomics 2016; 17: 184. doi: 10.1186/s12864-016-2529-1.
  34. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 2001; 25(4): 402-408.
  35. Sheldon IM, Owens SE. Postpartum uterine infection and endometritis in dairy cattle. Anim Reprod 2017; 14(3): 622-629.
  36. Liu J, Guo S, Jiang K, et al. miR‐488 mediates negative regulation of the AKT/NF‐κB pathway by targeting Rac1 in LPS‐induced inflammation. J Cell Physiol 2020; 235(5): 4766-4777.
  37. Farsimadan M, Ismail Haje M, Khudhur Mawlood C, et al. MicroRNA variants in endometriosis and its severity. Br J Biomed Sci 2021; 78(4): 206-210.
  38. Taganov KD, Boldin MP, Chang KJ, et al. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A 2006; 103(33): 12481-12486.
  39. Kasimanickam V, Kastelic J. Circulating cell-free mature microRNAs and their target gene prediction in bovine metritis. Sci Rep 2016; 6: 29509. doi: 10.1038/ srep29509.
  40. Herath S, Dobson H, Bryant CE, et al. Use of the cow as a large animal model of uterine infection and immunity. J Reprod Immunol 2006; 69(1): 13-22.
  41. Nahid MA, Satoh M, Chan EK. Mechanistic role of microRNA-146a in endotoxin-induced differential cross-regulation of TLR signaling. J Immunol 2011; 186(3): 1723-1734.
  42. Nahid MA, Pauley KM, Satoh M, et al. miR-146a is critical for endotoxin-induced tolerance: implication in innate immunity. J Biol Chem 2009; 284(50): 34590-34599.
  43. Ibrahim S, Szóstek-Mioduchowska A, Skarzynski D. Expression profiling of selected miRNAs in equine endometrium in response to LPS challenge in vitro: A new understanding of the inflammatory immune response. Vet Immunol Immunopathol 2019; 209: 37-44.
  44. Rabehi L, Irinopoulou T, Cholley B, et al. Gram-positive and gram-negative bacteria do not trigger monocytic cytokine production through similar intracellular pathways. Infect Immun 2001; 69(7): 4590-4599.
Veterinary Research Forum
Volume 14, Issue 8
August 2023
Pages 437-445

  • Receive Date 07 June 2022
  • Accept Date 01 August 2022

Home

Guide for Authors

Submit Manuscript

Reviewers

Contact Us