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Animals : an open access journal from MDPI2021; 11(11); 3151; doi: 10.3390/ani11113151

Equine Endometrosis Pathological Features: Are They Dependent on NF-κB Signaling Pathway?

Abstract: Endometrosis is an important mares' disease which considerably decreases their fertility. As classic endometrial classification methods might be insufficient for tissue pathological evaluation, further categorization into active/inactive and destructive/non-destructive types was developed by Hoffmann and others. This study aimed to compare NF-κB pathway genes transcription among histopathological types of endometrosis, following Hoffmann and co-authors' classification. Endometrial samples, collected postmortem from cyclic mares ( = 100) in estrus or diestrus, were classified histologically and used for gene transcription assessment. Gene transcription of NF-κB subunits (, , ), pro-inflammatory molecules (, ), and hyaluronan synthases (, , ) was compared among endometrosis types (active, non-active, destructive, non-destructive). Most individual mRNA samples showed high expression of , , and gene transcripts and the destructive type of endometrosis, simultaneously. The expression of and genes was higher in active destructive group than in the other groups only in the follicular phase, as well as being higher in the inactive destructive group than in the others, only in the mid-luteal phase. The increase in gene transcription of the NF-κB canonical activation pathway in destructive endometrosis may suggest the highest changes in extracellular matrix deposition. Moreover, the estrous cycle phase might influence fibrosis pathogenesis.
Publication Date: 2021-11-04 PubMed ID: 34827882PubMed Central: PMC8614257DOI: 10.3390/ani11113151Google Scholar: Lookup
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  • Journal Article

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.

This study investigates whether the transcription of certain genes in the NF-κB pathway differ between different pathological types of a mare fertility disease called endometrosis. Additionally, the research evaluates how the phase of the estrous cycle may influence this disease development.

Background

  • Endometrosis is a fertility disease in mares that is classified in various ways for pathological evaluation. Hoffmann and others introduced a classification method that separates the disease into active/inactive and destructive/non-destructive types.
  • This study focuses on the NF-κB pathway, a protein complex that plays a key role in regulating immune response to infection. It is often inactive in healthy cells and is activated to combat infection.

Purpose and Methods

  • The purpose of this study was to compare the transcription of genes in the NF-κB pathway among the different pathological types of endometrosis. This comparison was carried out based on Hoffmann’s classification method.
  • Endometrial samples were collected from mares in different stages of their estrous cycle and were then examined for gene transcription.

Findings

  • The results revealed that most of the mRNA samples showed high expression of certain gene transcripts, including those in the NF-κB subunits and pro-inflammatory molecules,
  • Such high expressions were mostly prevalent in the destructive type of endometrosis.
  • The expression of certain genes was higher in the active destructive group than in other groups, and this was only found in the follicular phase.

Conclusion

  • The study concludes that the transcription of genes in the NF-κB pathway may be influenced by the classification of endometrosis and the phase of the estrous cycle the mare is in.
  • It suggests that the highest changes in extracellular matrix deposition might correspond to the increased gene transcription in destructive endometrosis.

Cite This Article

APA
Jasiński T, Zdrojkowski Ł, Kautz E, Juszczuk-Kubiak E, Ferreira-Dias G, Domino M. (2021). Equine Endometrosis Pathological Features: Are They Dependent on NF-κB Signaling Pathway? Animals (Basel), 11(11), 3151. https://doi.org/10.3390/ani11113151

Publication

ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 11
Issue: 11
PII: 3151

Researcher Affiliations

Jasiński, Tomasz
  • Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.
Zdrojkowski, Łukasz
  • Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.
Kautz, Ewa
  • Department of Molecular Biology, Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, 05-552 Jastrzębiec, Poland.
Juszczuk-Kubiak, Edyta
  • Laboratory of Biotechnology and Molecular Engineering, Department of Microbiology, Prof. Wacław Dąbrowski Institute of Agricultural and Food Biotechnology-State Research Institute, 02-532 Warsaw, Poland.
Ferreira-Dias, Graça
  • Departmento de Morfologia e Função, CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-47 Lisbon, Portugal.
Domino, Małgorzata
  • Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.

Grant Funding

  • 2018/02/X/NZ4/00101 / National Science Center

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 36 references
  1. Hoffmann C, Ellenberger C, Mattos RC, Aupperle H, Dhein S, Stief B, Schoon HA. The equine endometrosis: new insights into the pathogenesis.. Anim Reprod Sci 2009 Apr;111(2-4):261-78.
  2. Schöniger S, Schoon HA. The Healthy and Diseased Equine Endometrium: A Review of Morphological Features and Molecular Analyses.. Animals (Basel) 2020 Apr 5;10(4).
    doi: 10.3390/ani10040625pmc: PMC7222714pubmed: 32260515google scholar: lookup
  3. Kenney RM, Doig PA. Equine endometrial biopsy. 1986;pp. 723–729.
  4. Lehmann J, Ellenberger C, Hoffmann C, Bazer FW, Klug J, Allen WR, Sieme H, Schoon HA. Morpho-functional studies regarding the fertility prognosis of mares suffering from equine endometrosis.. Theriogenology 2011 Oct 15;76(7):1326-36.
  5. Aupperle H, Schoon D, Schoon HA. Physiological and pathological expression of intermediate filaments in the equine endometrium.. Res Vet Sci 2004 Jun;76(3):249-55.
    doi: 10.1016/j.rvsc.2003.11.003pubmed: 15046960google scholar: lookup
  6. Bischofberger L, Szewczyk K, Schoon HA. Unequal glandular dierentiation of the equine endometrium—A separate endometrial alteration?. Pferdeheilkunde 2019;35:304–315.
    doi: 10.21836/PEM20190401google scholar: lookup
  7. Minkwitz C, Schoon HA, Zhang Q, Schöniger S. Plasticity of endometrial epithelial and stromal cells-A new approach towards the pathogenesis of equine endometrosis.. Reprod Domest Anim 2019 Jun;54(6):835-845.
    doi: 10.1111/rda.13431pubmed: 30907027google scholar: lookup
  8. Hoffmann C, Bazer FW, Klug J, Aupperle H, Ellenberger C, Schoon HA. Immunohistochemical and histochemical identification of proteins and carbohydrates in the equine endometrium Expression patterns for mares suffering from endometrosis.. Theriogenology 2009 Jan 15;71(2):264-74.
  9. Stewart F, Gerstenberg C, Suire S, Allen WR. Immunolocalization of a novel protein (P19) in the endometrium of fertile and subfertile mares.. J Reprod Fertil Suppl 2000;(56):593-9.
    pubmed: 20681174
  10. Schöniger S, Böttcher D, Theuß T, Gräfe H, Schoon HA. New insights into the innate immune defences of the equine endometrium: In situ and in vitro expression pattern of beta-defensin. Pferdeheilkunde 2016;32:4–14.
    doi: 10.21836/PEM20160101google scholar: lookup
  11. Schöniger S, Gräfe H, Richter F, Schoon HA. Expression of indoleamine 2,3-dioxygenase 1 as transcript and protein in the healthy and diseased equine endometrium.. Res Vet Sci 2018 Jun;118:278-287.
    doi: 10.1016/j.rvsc.2018.03.001pubmed: 29547726google scholar: lookup
  12. Schöniger S, Gräfe H, Schoon HA. Innate immunity mechanisms of the equine endometrium—Benefit or harm?. Pferdeheilkunde 2018;34:5–11.
    doi: 10.21836/PEM20180101google scholar: lookup
  13. Fouladi-Nashta AA, Raheem KA, Marei WF, Ghafari F, Hartshorne GM. Regulation and roles of the hyaluronan system in mammalian reproduction.. Reproduction 2017 Feb;153(2):R43-R58.
    doi: 10.1530/REP-16-0240pubmed: 27799626google scholar: lookup
  14. Itano N, Sawai T, Yoshida M, Lenas P, Yamada Y, Imagawa M, Shinomura T, Hamaguchi M, Yoshida Y, Ohnuki Y, Miyauchi S, Spicer AP, McDonald JA, Kimata K. Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties.. J Biol Chem 1999 Aug 27;274(35):25085-92.
    doi: 10.1074/jbc.274.35.25085pubmed: 10455188google scholar: lookup
  15. Stern R. Hyaluronan catabolism: a new metabolic pathway.. Eur J Cell Biol 2004 Aug;83(7):317-25.
    doi: 10.1078/0171-9335-00392pubmed: 15503855google scholar: lookup
  16. Walter I, Handler J, Miller I, Aurich C. Matrix metalloproteinase 2 (MMP-2) and tissue transglutaminase (TG 2) are expressed in periglandular fibrosis in horse mares with endometrosis.. Histol Histopathol 2005 Oct;20(4):1105-13.
    pubmed: 16136493doi: 10.14670/hh-20.1105google scholar: lookup
  17. Rodriguez Hurtado I, Stewart AJ, Wolfe DF, Caldwell FJ, Harrie M, Whitley EM. Immunolocalization of the hyaluronan receptor CD44 in the reproductive tract of the mare.. Theriogenology 2011 Jan 15;75(2):276-86.
  18. Rebordão MR, Galvão A, Szóstek A, Amaral A, Mateus L, Skarzynski DJ, Ferreira-Dias G. Physiopathologic mechanisms involved in mare endometrosis.. Reprod Domest Anim 2014 Oct;49 Suppl 4:82-7.
    doi: 10.1111/rda.12397pubmed: 25277436google scholar: lookup
  19. Rebordão MR, Amaral A, Lukasik K, Szóstek-Mioduchowska A, Pinto-Bravo P, Galvão A, Skarzynski DJ, Ferreira-Dias G. Constituents of neutrophil extracellular traps induce in vitro collagen formation in mare endometrium.. Theriogenology 2018 Jun;113:8-18.
  20. Domino M, Jasinski T, Kautz E, Juszczuk-Kubiak E, Ferreira-Dias G, Zabielski R, Sady M, Gajewski Z. Expression of genes involved in the NF-κB-dependent pathway of the fibrosis in the mare endometrium.. Theriogenology 2020 Apr 15;147:18-24.
  21. Szóstek-Mioduchowska A, Słowińska M, Pacewicz J, Skarzynski DJ, Okuda K. Matrix metallopeptidase expression and modulation by transforming growth factor-β1 in equine endometrosis.. Sci Rep 2020 Jan 24;10(1):1119.
    doi: 10.1038/s41598-020-58109-0pmc: PMC6981191pubmed: 31980722google scholar: lookup
  22. Ahn BN, Song MH, Kim JH, Kim KH, Park KK, Choi YS. Intra-peritoneal NF-kappaB decoy oligodeoxynucleotide decreases postoperative intra-abdominal adhesion. Korean J. Obstet. Gynecol. 2012;55:244–249.
  23. Sosińska P, Baum E, Maćkowiak B, Staniszewski R, Jasinski T, Umezawa K, Bręborowicz A. Inhibition of NF-kappaB with Dehydroxymethylepoxyquinomicin modifies the function of human peritoneal mesothelial cells.. Am J Transl Res 2016;8(12):5756-5765.
    pmc: PMC5209527pubmed: 28078047
  24. Alekseevna RV, Pavlovich DA, Evgenievich BY, Viktorovich NS. Nuclear factor kappa B as a potential target for pharmacological correction endothelium-associated pathology. Res. Res. Pharm. 2017;3:114–124.
  25. Arjmand MH. The association between visceral adiposity with systemic inflammation, oxidative stress, and risk of post-surgical adhesion.. Arch Physiol Biochem 2022 Aug;128(4):869-874.
    doi: 10.1080/13813455.2020.1733617pubmed: 32141779google scholar: lookup
  26. Dejban P, Nikravangolsefid N, Chamanara M, Dehpour A, Rashidian A. The role of medicinal products in the treatment of inflammatory bowel diseases (IBD) through inhibition of TLR4/NF-kappaB pathway.. Phytother Res 2021 Feb;35(2):835-845.
    doi: 10.1002/ptr.6866pubmed: 32929778google scholar: lookup
  27. May MJ, Ghosh S. Signal transduction through NF-kappa B.. Immunol Today 1998 Feb;19(2):80-8.
    doi: 10.1016/S0167-5699(97)01197-3pubmed: 9509763google scholar: lookup
  28. Lind DS, Hochwald SN, Malaty J, Rekkas S, Hebig P, Mishra G, Moldawer LL, Copeland EM 3rd, Mackay S. Nuclear factor-kappa B is upregulated in colorectal cancer.. Surgery 2001 Aug;130(2):363-9.
    doi: 10.1067/msy.2001.116672pubmed: 11490372google scholar: lookup
  29. Umezawa K. Possible role of peritoneal NF-κB in peripheral inflammation and cancer: lessons from the inhibitor DHMEQ.. Biomed Pharmacother 2011 Jul;65(4):252-9.
    doi: 10.1016/j.biopha.2011.02.003pubmed: 21723080google scholar: lookup
  30. Roberto da Costa RP, Serrão PM, Monteiro S, Pessa P, Silva JR, Ferreira-Dias G. Caspase-3-mediated apoptosis and cell proliferation in the equine endometrium during the oestrous cycle.. Reprod Fertil Dev 2007;19(8):925-32.
    doi: 10.1071/RD06159pubmed: 18076824google scholar: lookup
  31. Schoon HA, Schoon D, Klug E. Die Endometriumbiopsie bei der Stute im klinisch-gynäkologischen Kontext. Pferdeheilkunde 1997;13:453–464.
    doi: 10.21836/PEM19970506google scholar: lookup
  32. Brasier AR. The nuclear factor-kappaB-interleukin-6 signalling pathway mediating vascular inflammation.. Cardiovasc Res 2010 May 1;86(2):211-8.
    doi: 10.1093/cvr/cvq076pmc: PMC2912657pubmed: 20202975google scholar: lookup
  33. Ohkawa T, Ueki N, Taguchi T, Shindo Y, Adachi M, Amuro Y, Hada T, Higashino K. Stimulation of hyaluronan synthesis by tumor necrosis factor-alpha is mediated by the p50/p65 NF-kappa B complex in MRC-5 myofibroblasts.. Biochim Biophys Acta 1999 Jan 11;1448(3):416-24.
    doi: 10.1016/S0167-4889(98)00155-4pubmed: 9990294google scholar: lookup
  34. Caon I, Bartolini B, Moretto P, Parnigoni A, Caravà E, Vitale DL, Alaniz L, Viola M, Karousou E, De Luca G, Hascall VC, Passi A, Vigetti D. Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2-AS1.. J Biol Chem 2020 Mar 13;295(11):3485-3496.
    doi: 10.1074/jbc.RA119.011982pmc: PMC7076221pubmed: 31932306google scholar: lookup
  35. Tong W, Geng Y, Huang Y, Shi Y, Xiang S, Zhang N, Qin L, Shi Q, Chen Q, Dai K, Zhang X. In Vivo Identification and Induction of Articular Cartilage Stem Cells by Inhibiting NF-κB Signaling in Osteoarthritis.. Stem Cells 2015 Oct;33(10):3125-37.
    doi: 10.1002/stem.2124pubmed: 26285913google scholar: lookup
  36. Chung S, Kim S, Son M, Kim M, Koh ES, Shin SJ, Park CW, Kim HS. Inhibition of p300/CBP-Associated Factor Attenuates Renal Tubulointerstitial Fibrosis through Modulation of NF-kB and Nrf2.. Int J Mol Sci 2019 Mar 28;20(7).
    doi: 10.3390/ijms20071554pmc: PMC6479343pubmed: 30925687google scholar: lookup

Citations

This article has been cited 9 times.
  1. Laseca N, Cánovas Á, Valera M, Id-Lahoucine S, Perdomo-González DI, Fonseca PAS, Demyda-Peyrás S, Molina A. Genomic screening of allelic and genotypic transmission ratio distortion in horse. PLoS One 2023;18(8):e0289066.
    doi: 10.1371/journal.pone.0289066pubmed: 37556504google scholar: lookup
  2. Zdrojkowski Ł, Jasiński T, Ferreira-Dias G, Pawliński B, Domino M. The Role of NF-κB in Endometrial Diseases in Humans and Animals: A Review. Int J Mol Sci 2023 Feb 2;24(3).
    doi: 10.3390/ijms24032901pubmed: 36769226google scholar: lookup
  3. Jasiński T, Zdrojkowski Ł, Ferreira-Dias G, Kautz E, Juszczuk-Kubiak E, Domino M. Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors' Dysfunction. Int J Mol Sci 2022 Jul 1;23(13).
    doi: 10.3390/ijms23137360pubmed: 35806363google scholar: lookup
  4. Katila T, Ferreira-Dias G. Evolution of the Concepts of Endometrosis, Post Breeding Endometritis, and Susceptibility of Mares. Animals (Basel) 2022 Mar 19;12(6).
    doi: 10.3390/ani12060779pubmed: 35327176google scholar: lookup
  5. Jasiński T, Zdrojkowski Ł, Kautz E, Juszczuk-Kubiak E, Ferreira-Dias G, Domino M. The NF-κB-signalling pathway in mare's endometrium infiltrated with the inflammatory cells. Reprod Domest Anim 2022 Jun;57(6):598-610.
    doi: 10.1111/rda.14099pubmed: 35182075google scholar: lookup
  6. Khan MZ, Chen W, Liu X, Kou X, Khan A, Khan RU, Zahoor M, Wang C. An Overview of Bioactive Compounds' Role in Modulating the Nrf2/Keap1/NF-κB Pathway to Alleviate Lipopolysaccharide-Induced Endometritis. Int J Mol Sci 2024 Sep 25;25(19).
    doi: 10.3390/ijms251910319pubmed: 39408650google scholar: lookup
  7. Li H, Li Y, Luo S, Zhang Y, Feng Z, Li S. The roles and mechanisms of the NF-κB signaling pathway in tendon disorders. Front Vet Sci 2024;11:1382239.
    doi: 10.3389/fvets.2024.1382239pubmed: 38978635google scholar: lookup
  8. Zdrojkowski Ł, Pawliński B, Skierbiszewska K, Jasiński T, Domino M. Assessment of Connective Tissue in the Equine Uterus and Cervix: Review of Clinical Impact and Staining Options. Animals (Basel) 2024 Jan 3;14(1).
    doi: 10.3390/ani14010156pubmed: 38200887google scholar: lookup
  9. Wong YS, Mançanares AC, Navarrete FI, Poblete PM, Méndez-Pérez L, Ferreira-Dias GML, Rodriguez-Alvarez L, Castro FO. Mare stromal endometrial cells differentially modulate inflammation depending on oestrus cycle status: an in vitro study. Front Vet Sci 2023;10:1271240.
    doi: 10.3389/fvets.2023.1271240pubmed: 37869492google scholar: lookup