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Theriogenology2003; 60(2); 209-223; doi: 10.1016/s0093-691x(02)01376-6

Development and comparison of in vivo and in vitro models for endometritis in cows and mares.

Abstract: In order to investigate pathogenic mechanisms of acute endometritis in cows and mares, we established an in vivo model in both species. Based on the results of an in vitro transmigration system, human recombinant interleukin-8 (rhIL-8; 1.25 microg per mare and 5 microg per cow in 50 ml phosphate-buffered saline) was used to attract polymorphonuclear neutrophil granulocytes (PMNs) into the uteri. Peak numbers of uterine neutrophils were attracted after 6h, in both cows and mares. On average, mares responded more sensitively than cows, with 15 times higher numbers of rhIL-8-attracted uterine neutrophils (72+/-8 x 10(7)cells). In contrast to in vitro studies, in vivo migrated neutrophils (uterine neutrophils) of both species displayed a significantly reduced MHC class I expression. Expression of the CD11a molecule was significantly enhanced on equine uterine neutrophils but downregulated on bovine cells. Compared with untreated autologous peripheral neutrophils, both uterine and in vitro migrated neutrophils showed no alteration of phagocytic capacity. The ability to generate reactive oxygen species (ROS) was significantly upregulated in bovine and equine uterine neutrophils. This was also observed after in vitro migration of equine neutrophils, whereas ROS generation by bovine neutrophils was significantly depressed. In summary, the concept of inducing endometritis directly by local application of human interleukin-8 has been reliably successful in cows and mares. The model permits the analysis of PMN migration into the uterus under defined and controlled conditions. The observed differences between cows and mares with respect to phenotypical and functional characteristics of in vivo attracted uterine cells point to species-related features of neutrophil migration. In vitro transmigrated bovine and equine cells partially differ in phenotype and function from uterine neutrophils. Therefore, the in vitro transmigration assay cannot completely represent the in vivo endometritis model described here.
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Publication Date: 2003-05-17 PubMed ID: 12749935DOI: 10.1016/s0093-691x(02)01376-6Google Scholar: Lookup
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  • Journal Article
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article concerns the development and comparison of in vivo and in vitro models for endometritis in cows and mares. The aim was to understand the mechanisms of acute endometritis in these animals. The study found differences in how cows and mares respond to the condition, and also noticed discrepancies between the in vivo and in vitro models.

Establishment of In Vivo Models

  • The researchers established an in vivo model for both cows and mares to study acute endometritis, which is inflammation of the inner lining of the uterus.
  • Human recombinant interleukin-8 (rhIL-8), an agent known to attract immune cells called polymorphonuclear neutrophil granulocytes (PMNs), was introduced into the UTI to study how these cells respond in the uterus environment. The rhIL-8 dosage was specified depending on the species (1.25 micrograms for mares and 5 micrograms for cows).
  • Both cows and mares exhibited peak numbers of UTI neutrophils after 6 hours. It was observed that mares were more sensitive than cows, with 15 times higher neutrophil count.

Neutrophil Characteristics

  • In contrast with in vitro studies, in vivo migrated neutrophils of both cows and mares showed significantly reduced MHC class I expression.
  • Differentiation was observed in the expression of the CD11a molecule between the two species; it was enhanced in equine uterine neutrophils but downregulated in bovine cells.
  • Both the uterine and in vitro migrated neutrophils displayed no change in their capacity to engulf and digest particles (phagocytic capacity).
  • The ability to generate reactive oxygen species (ROS) was significantly upregulated in uterine neutrophils of both species. However, in the case of in vitro migration, bovine neutrophils showed a significant depression in ROS generation.

Outcome and Implications

  • Overall, the in vivo model successfully induced endometritis in both cows and mares using human interleukin-8, allowing for the analysis of neutrophil migration into the uterus under controlled conditions.
  • The observed differences between cows and mares in terms of immune response to affliction point to species-related features of neutrophil migration.
  • The researchers concluded that the in vitro migration model doesn’t completely represent the in vivo endometritis model because of observable differences in the appearance and function of the migrated cells in the two situations.

Cite This Article

APA
Zerbe H, Schuberth HJ, Engelke F, Frank J, Klug E, Leibold W. (2003). Development and comparison of in vivo and in vitro models for endometritis in cows and mares. Theriogenology, 60(2), 209-223. https://doi.org/10.1016/s0093-691x(02)01376-6

Publication

Theriogenology
ISSN: 0093-691X
NlmUniqueID: 0421510
Country: United States
Language: English
Volume: 60
Issue: 2
Pages: 209-223

Researcher Affiliations

Zerbe, H
  • Clinic for Bovine Obstetrics and Gynecology, School of Veterinary Medicine, Bischofsholer Damm 15, D-30173 Hannover, Germany. Holm.Zerbe@tiho-hannover.de
Schuberth, H-J
    Engelke, F
      Frank, J
        Klug, E
          Leibold, W

            MeSH Terms

            • Animals
            • CD11a Antigen / analysis
            • Cattle
            • Cattle Diseases / metabolism
            • Cattle Diseases / pathology
            • Chemotaxis, Leukocyte
            • Disease Models, Animal
            • Endometritis / veterinary
            • Female
            • Histocompatibility Antigens Class I / analysis
            • Horse Diseases / metabolism
            • Horse Diseases / pathology
            • Horses
            • Humans
            • Interleukin-8 / administration & dosage
            • Leukocyte Count
            • Neutrophils / pathology
            • Reactive Oxygen Species
            • Recombinant Proteins / administration & dosage
            • Time Factors
            • Uterus / pathology

            Citations

            This article has been cited 24 times.
            1. Li H, Liu L, Wang J, Zhao W. The emerging role of neutrophil extracellular traps in endometritis.. Front Immunol 2023;14:1153851.
              doi: 10.3389/fimmu.2023.1153851pubmed: 37033951google scholar: lookup
            2. Shen W, Ma X, Shao D, Wu X, Wang S, Zheng J, Lv Y, Ding X, Ma B, Yan Z. Neutrophil Extracellular Traps Mediate Bovine Endometrial Epithelial Cell Pyroptosis in Dairy Cows with Endometritis.. Int J Mol Sci 2022 Nov 13;23(22).
              doi: 10.3390/ijms232214013pubmed: 36430491google scholar: lookup
            3. Drillich M, Wagener K. Pathogenesis of uterine diseases in dairy cattle and implications for fertility.. Anim Reprod 2018 Jul-Sep;15(Suppl 1):879-885.
              doi: 10.21451/1984-3143-AR2018-0023pubmed: 36249851google scholar: lookup
            4. Boni R, Cecchini Gualandi S. Relationship between Oxidative Stress and Endometritis: Exploiting Knowledge Gained in Mares and Cows.. Animals (Basel) 2022 Sep 13;12(18).
              doi: 10.3390/ani12182403pubmed: 36139263google scholar: lookup
            5. Chotimanukul S, Suwimonteerabutr J, Techakumphu M, Swangchan-Uthai T. In Vitro Effects of Short-Term and Long-Term Heat Exposures on the Immune Response and Prostaglandin Biosynthesis in Bovine Endometrial Cells.. Animals (Basel) 2022 Sep 9;12(18).
              doi: 10.3390/ani12182359pubmed: 36139219google scholar: lookup
            6. Shen W, Oladejo AO, Ma X, Jiang W, Zheng J, Imam BH, Wang S, Wu X, Ding X, Ma B, Yan Z. Inhibition of Neutrophil Extracellular Traps Formation by Cl-Amidine Alleviates Lipopolysaccharide-Induced Endometritis and Uterine Tissue Damage.. Animals (Basel) 2022 Apr 29;12(9).
              doi: 10.3390/ani12091151pubmed: 35565576google scholar: lookup
            7. Tan X, Zhang L, Li T, Zhan J, Qiao K, Wu H, Sun S, Huang M, Zhang F, Zhang M, Li C, Li R, Pan H. Lgr4 Regulates Oviductal Epithelial Secretion Through the WNT Signaling Pathway.. Front Cell Dev Biol 2021;9:666303.
              doi: 10.3389/fcell.2021.666303pubmed: 34631693google scholar: lookup
            8. Wagener K, Drillich M, Aurich C, Gabler C. Endometrial Inflammation at the Time of Insemination and Its Effect on Subsequent Fertility of Dairy Cows.. Animals (Basel) 2021 Jun 22;11(7).
              doi: 10.3390/ani11071858pubmed: 34206536google scholar: lookup
            9. Segabinazzi LGTM, Canisso IF, Podico G, Cunha LL, Novello G, Rosser MF, Loux SC, Lima FS, Alvarenga MA. Intrauterine Blood Plasma Platelet-Therapy Mitigates Persistent Breeding-Induced Endometritis, Reduces Uterine Infections, and Improves Embryo Recovery in Mares.. Antibiotics (Basel) 2021 Apr 23;10(5).
              doi: 10.3390/antibiotics10050490pubmed: 33922743google scholar: lookup
            10. Manosalva C, Quiroga J, Teuber S, Cárdenas S, Carretta MD, Morán G G, Alarcón P, Hidalgo MA, Burgos RA. D-Lactate Increases Cytokine Production in Bovine Fibroblast-Like Synoviocytes via MCT1 Uptake and the MAPK, PI3K/Akt, and NFκB Pathways.. Animals (Basel) 2020 Nov 13;10(11).
              doi: 10.3390/ani10112105pubmed: 33202791google scholar: lookup
            11. Marey MA, Aboul Ezz M, Akthar I, Yousef MS, Imakawa K, Shimada M, Miyamoto A. Sensing sperm via maternal immune system: a potential mechanism for controlling microenvironment for fertility in the cow.. J Anim Sci 2020 Aug 18;98(Suppl 1):S88-S95.
              doi: 10.1093/jas/skaa147pubmed: 32810249google scholar: lookup
            12. Mikulková K, Kadek R, Filípek J, Illek J. Evaluation of oxidant/antioxidant status, metabolic profile and milk production in cows with metritis.. Ir Vet J 2020;73:8.
              doi: 10.1186/s13620-020-00161-3pubmed: 32514335google scholar: lookup
            13. Bhadaniya AR, Prasad MC, Savsani HH, Kalaria VA, Fefar DT, Mathpati BS, Javia BB. Pro-inflammatory cytokine expression studies of subclinical and clinical endometritis in endometrial tissues of buffaloes.. Trop Anim Health Prod 2019 Jun;51(5):1161-1166.
              doi: 10.1007/s11250-019-01802-8pubmed: 30684222google scholar: lookup
            14. Alhussien MN, Dang AK. Potential roles of neutrophils in maintaining the health and productivity of dairy cows during various physiological and physiopathological conditions: a review.. Immunol Res 2019 Feb;67(1):21-38.
              doi: 10.1007/s12026-019-9064-5pubmed: 30644032google scholar: lookup
            15. Adnane M, Meade KG, O'Farrelly C. Cervico-vaginal mucus (CVM) - an accessible source of immunologically informative biomolecules.. Vet Res Commun 2018 Dec;42(4):255-263.
              doi: 10.1007/s11259-018-9734-0pubmed: 30117040google scholar: lookup
            16. Danesh Mesgaran S, Sharbati J, Einspanier R, Gabler C. mRNA expression pattern of selected candidate genes differs in bovine oviductal epithelial cells in vitro compared with the in vivo state and during cell culture passages.. Reprod Biol Endocrinol 2016 Aug 15;14(1):44.
              doi: 10.1186/s12958-016-0176-7pubmed: 27526775google scholar: lookup
            17. Manimaran A, Kumaresan A, Jeyakumar S, Mohanty TK, Sejian V, Kumar N, Sreela L, Prakash MA, Mooventhan P, Anantharaj A, Das DN. Potential of acute phase proteins as predictor of postpartum uterine infections during transition period and its regulatory mechanism in dairy cattle.. Vet World 2016 Jan;9(1):91-100.
              doi: 10.14202/vetworld.2016.91-100pubmed: 27051191google scholar: lookup
            18. Cronin JG, Turner ML, Goetze L, Bryant CE, Sheldon IM. Toll-like receptor 4 and MYD88-dependent signaling mechanisms of the innate immune system are essential for the response to lipopolysaccharide by epithelial and stromal cells of the bovine endometrium.. Biol Reprod 2012 Feb;86(2):51.
              doi: 10.1095/biolreprod.111.092718pubmed: 22053092google scholar: lookup
            19. Gabler C, Fischer C, Drillich M, Einspanier R, Heuwieser W. Time-dependent mRNA expression of selected pro-inflammatory factors in the endometrium of primiparous cows postpartum.. Reprod Biol Endocrinol 2010 Dec 22;8:152.
              doi: 10.1186/1477-7827-8-152pubmed: 21176181google scholar: lookup
            20. Sheldon IM, Rycroft AN, Dogan B, Craven M, Bromfield JJ, Chandler A, Roberts MH, Price SB, Gilbert RO, Simpson KW. Specific strains of Escherichia coli are pathogenic for the endometrium of cattle and cause pelvic inflammatory disease in cattle and mice.. PLoS One 2010 Feb 12;5(2):e9192.
              doi: 10.1371/journal.pone.0009192pubmed: 20169203google scholar: lookup
            21. Herath S, Lilly ST, Santos NR, Gilbert RO, Goetze L, Bryant CE, White JO, Cronin J, Sheldon IM. Expression of genes associated with immunity in the endometrium of cattle with disparate postpartum uterine disease and fertility.. Reprod Biol Endocrinol 2009 May 29;7:55.
              doi: 10.1186/1477-7827-7-55pubmed: 19476661google scholar: lookup
            22. 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 cattle.. Biol Reprod 2009 Dec;81(6):1025-32.
              doi: 10.1095/biolreprod.109.077370pubmed: 19439727google scholar: lookup
            23. Sheldon IM, Williams EJ, Miller AN, Nash DM, Herath S. Uterine diseases in cattle after parturition.. Vet J 2008 Apr;176(1):115-21.
              doi: 10.1016/j.tvjl.2007.12.031pubmed: 18329302google scholar: lookup
            24. Herath S, Fischer DP, Werling D, Williams EJ, Lilly ST, Dobson H, Bryant CE, Sheldon IM. Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus.. Endocrinology 2006 Jan;147(1):562-70.
              doi: 10.1210/en.2005-1113pubmed: 16223858google scholar: lookup
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