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Home / Equine Research Bank / J Reprod Dev / Expression of endometrial immune-related genes possibly func...
The Journal of reproduction and development2012; 59(1); 85-91; doi: 10.1262/jrd.2012-142

Expression of endometrial immune-related genes possibly functioning during early pregnancy in the mare.

Abstract: Despite enormous efforts, biochemical and molecular mechanisms associated with equine reproduction, particularly processes of pregnancy establishment, have not been well characterized. Previously, PCR-selected suppression subtraction hybridization analysis was executed to identify unique molecules functioning in the equine endometrium during periods of pregnancy establishment, and granzyme B (GZMB) cDNA was found in the pregnant endometrial cDNA library. Because GZMB is produced from natural killer (NK) cells, endometrial expression of GZMB and immune-related transcripts were characterized in this study. The level of GZMB mRNA is higher in the pregnant endometrium than in non-pregnant ones. This expression was also confirmed through Western blot and immunohistochemical analyses. IL-2 mRNA declined as pregnancy progressed, while IL-15, IFNG and TGFB1 transcripts increased on day 19 and/or 25. Analyses of IL-4 and IL-12 mRNAs demonstrated the increase in these transcripts as pregnancy progressed. Increase in CCR5 and CCR4 mRNAs indicated that both Th1 and Th2 cells coexisted in the day 25 pregnant endometrium. Taken together, the endometrial expression of immune-related transcripts suggests that immunological responses are present even before the trophectoderm actually attaches to the uterine epithelial cells.
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Publication Date: 2012-11-09 PubMed ID: 23138119PubMed Central: PMC3943239DOI: 10.1262/jrd.2012-142Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • 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 explores the expression levels of various immune-related genes in horses during early pregnancy, highlighting an increase in Granzyme B (GZMB) mRNA and other transcripts prevalent in the gestational endometrium.

Objectives of the Research

  • This study was conducted to understand and characterize the molecular mechanisms involved in equine reproduction, particularly during the establishment of pregnancy.
  • Of specific interest was the expression of GZMB cDNA and other immune-related transcripts in the pregnant endometrium.

Key Observations

  • The research found that the level of GZMB mRNA, an enzyme produced by natural killer (NK) cells, is higher in the pregnant endometrium compared to the non-pregnant ones. This was also confirmed in Western blot and immunohistochemical analyses.
  • They also found that mRNA for Interleukin-2 (IL-2), IL-15, interferon gamma (IFNG), and transforming growth factor-beta 1 (TGFB1) variously increase or decrease during pregnancy progression.
  • IL-4 and IL-12 mRNA levels increased as pregnancy went on, while Chemokine Receptor 5 (CCR5) and Chemokine Receptor 4 (CCR4) mRNA levels increased as well.

Implication of the Results

  • The data suggests that there exists immunological responses even before the embryonic trophectoderm attaches to the uterine epithelia cells during the early stages of pregnancy.
  • This also sheds light on the coexistence of Th1 and Th2 cells in the gestational day 25 pregnant endometrium, as indicated by the increased mRNA levels of both CCR5 and CCR4.

Conclusion

  • The research provides more detail as to the biochemical and molecular mechanisms involved in equine pregnancy establishment.
  • The endometrial expression of immune-related transcripts helps to increase the understanding of the relationship between immunology and early equine pregnancy.

Cite This Article

APA
Tachibana Y, Nakano Y, Nagaoka K, Kikuchi M, Nambo Y, Haneda S, Matsui M, Miyake Y, Imakawa K. (2012). Expression of endometrial immune-related genes possibly functioning during early pregnancy in the mare. J Reprod Dev, 59(1), 85-91. https://doi.org/10.1262/jrd.2012-142

Publication

The Journal of reproduction and development
ISSN: 1348-4400
NlmUniqueID: 9438792
Country: Japan
Language: English
Volume: 59
Issue: 1
Pages: 85-91

Researcher Affiliations

Tachibana, Yurika
  • Laboratory of Animal Breeding, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
Nakano, Yasuko
    Nagaoka, Kentaro
      Kikuchi, Masato
        Nambo, Yasuo
          Haneda, Shingo
            Matsui, Motozumi
              Miyake, Yo-Ichi
                Imakawa, Kazuhiko

                  MeSH Terms

                  • Animals
                  • Cell Movement
                  • Embryo Implantation
                  • Endometrium / immunology
                  • Endometrium / metabolism
                  • Female
                  • Gene Expression Regulation, Developmental
                  • Gene Library
                  • Granzymes / metabolism
                  • Horses
                  • Immunohistochemistry
                  • In Situ Hybridization
                  • Interleukin-12 / metabolism
                  • Interleukin-4 / metabolism
                  • Polymerase Chain Reaction
                  • Pregnancy
                  • Pregnancy, Animal
                  • RNA, Messenger / metabolism

                  References

                  This article includes 37 references
                  1. Hunt K. Horse Evolution. TalkOringins Archive 1995.
                  2. Ginther OJ. Reproductive Biology of the Mare: Basic and Applied Aspects, 2nd ed.. Cross Plains: Equiservices; 1992.
                  3. Allen WR. The physiology of early pregnancy in the mare. AAEP Proceedings 2000; 46: 338–354.
                  4. Haneda S, Nagaoka K, Nambo Y, Kikuchi M, Nakano Y, Matsui M, Miyake Y, Macleod JN, Imakawa K. Interleukin-1 receptor antagonist expression in the equine endometrium during the peri-implantation period.. Domest Anim Endocrinol 2009 May;36(4):209-18.
                    pubmed: 19157767doi: 10.1016/j.domaniend.2008.11.006google scholar: lookup
                  5. Liu CC, Persechini PM, Young JD. Perforin and lymphocyte-mediated cytolysis.. Immunol Rev 1995 Aug;146:145-75.
                    pubmed: 7493752doi: 10.1111/j.1600-065x.1995.tb00688.xgoogle scholar: lookup
                  6. Trapani JA. Granzymes: a family of lymphocyte granule serine proteases.. Genome Biol 2001;2(12):REVIEWS3014.
                    pmc: PMC138995pubmed: 11790262doi: 10.1186/gb-2001-2-12-reviews3014google scholar: lookup
                  7. Jokhi PP, King A, Sharkey AM, Smith SK, Loke YW. Screening for cytokine messenger ribonucleic acids in purified human decidual lymphocyte populations by the reverse-transcriptase polymerase chain reaction.. J Immunol 1994 Nov 15;153(10):4427-35.
                    pubmed: 7525703
                  8. Jokhi PP, King A, Loke YW. Cytokine production and cytokine receptor expression by cells of the human first trimester placental-uterine interface.. Cytokine 1997 Feb;9(2):126-37.
                    pubmed: 9071564doi: 10.1006/cyto.1996.0146google scholar: lookup
                  9. Rieger L, Kämmerer U, Hofmann J, Sütterlin M, Dietl J. Choriocarcinoma cells modulate the cytokine production of decidual large granular lymphocytes in coculture.. Am J Reprod Immunol 2001 Aug;46(2):137-43.
                    pubmed: 11506078doi: 10.1111/j.8755-8920.2001.460204.xgoogle scholar: lookup
                  10. Eriksson M, Meadows SK, Wira CR, Sentman CL. Unique phenotype of human uterine NK cells and their regulation by endogenous TGF-beta.. J Leukoc Biol 2004 Sep;76(3):667-75.
                    pubmed: 15178706doi: 10.1189/jlb.0204090google scholar: lookup
                  11. Kitaya K, Yasuda J, Yagi I, Tada Y, Fushiki S, Honjo H. IL-15 expression at human endometrium and decidua.. Biol Reprod 2000 Sep;63(3):683-7.
                    pubmed: 10952908doi: 10.1095/biolreprod63.3.683google scholar: lookup
                  12. Kelly RW, King AE, Critchley HO. Cytokine control in human endometrium.. Reproduction 2001 Jan;121(1):3-19.
                    pubmed: 11226025doi: 10.1530/rep.0.1210003google scholar: lookup
                  13. Chaouat G, Zourbas S, Ostojic S, Lappree-Delage G, Dubanchet S, Ledee N, Martal J. A brief review of recent data on some cytokine expressions at the materno-foetal interface which might challenge the classical Th1/Th2 dichotomy.. J Reprod Immunol 2002 Jan;53(1-2):241-56.
                    pubmed: 11730920doi: 10.1016/s0165-0378(01)00119-xgoogle scholar: lookup
                  14. Golander A, Barrett JR, Tyrey L, Fletcher WH, Handwerger S. Differential synthesis of human placental lactogen and human chorionic gonadotropin in vitro.. Endocrinology 1978 Feb;102(2):597-605.
                    pubmed: 743981doi: 10.1210/endo-102-2-597google scholar: lookup
                  15. Maslar IA, Riddick DH. Prolactin production by human endometrium during the normal menstrual cycle.. Am J Obstet Gynecol 1979 Nov 15;135(6):751-4.
                    pubmed: 495675doi: 10.1016/0002-9378(79)90386-7google scholar: lookup
                  16. Okada S, Okada H, Sanezumi M, Nakajima T, Yasuda K, Kanzaki H. Expression of interleukin-15 in human endometrium and decidua.. Mol Hum Reprod 2000 Jan;6(1):75-80.
                    pubmed: 10611264doi: 10.1093/molehr/6.1.75google scholar: lookup
                  17. Chegini N, Ma C, Roberts M, Williams RS, Ripps BA. Differential expression of interleukins (IL) IL-13 and IL-15 throughout the menstrual cycle in endometrium of normal fertile women and women with recurrent spontaneous abortion.. J Reprod Immunol 2002 Jul-Aug;56(1-2):93-110.
                    pubmed: 12106886doi: 10.1016/s0165-0378(02)00043-8google scholar: lookup
                  18. Dunn CL, Critchley HO, Kelly RW. IL-15 regulation in human endometrial stromal cells.. J Clin Endocrinol Metab 2002 Apr;87(4):1898-901.
                    pubmed: 11932337doi: 10.1210/jcem.87.4.8539google scholar: lookup
                  19. Bellone G, Aste-Amezaga M, Trinchieri G, Rodeck U. Regulation of NK cell functions by TGF-beta 1.. J Immunol 1995 Aug 1;155(3):1066-73.
                    pubmed: 7636180
                  20. Naganuma H, Sasaki A, Satoh E, Nagasaka M, Nakano S, Isoe S, Tasaka K, Nukui H. Transforming growth factor-beta inhibits interferon-gamma secretion by lymphokine-activated killer cells stimulated with tumor cells.. Neurol Med Chir (Tokyo) 1996 Nov;36(11):789-95.
                    pubmed: 9420430doi: 10.2176/nmc.36.789google scholar: lookup
                  21. Seo N, Tokura Y, Takigawa M, Egawa K. Depletion of IL-10- and TGF-beta-producing regulatory gamma delta T cells by administering a daunomycin-conjugated specific monoclonal antibody in early tumor lesions augments the activity of CTLs and NK cells.. J Immunol 1999 Jul 1;163(1):242-9.
                    pubmed: 10384122
                  22. Castriconi R, Cantoni C, Della Chiesa M, Vitale M, Marcenaro E, Conte R, Biassoni R, Bottino C, Moretta L, Moretta A. Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells.. Proc Natl Acad Sci U S A 2003 Apr 1;100(7):4120-5.
                    pmc: PMC153058pubmed: 12646700doi: 10.1073/pnas.0730640100google scholar: lookup
                  23. Hayashi H, Inoue Y, Tsutsui H, Okamura H, Nakanishi K, Onozaki K. TGFbeta down-regulates IFN-gamma production in IL-18 treated NK cell line LNK5E6.. Biochem Biophys Res Commun 2003 Jan 24;300(4):980-5.
                    pubmed: 12559970doi: 10.1016/s0006-291x(02)02939-xgoogle scholar: lookup
                  24. Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-Mon M, Derynck R, Sporn MB, Fauci AS. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.. J Exp Med 1986 May 1;163(5):1037-50.
                    pmc: PMC2188095pubmed: 2871125doi: 10.1084/jem.163.5.1037google scholar: lookup
                  25. Ruegemer JJ, Ho SN, Augustine JA, Schlager JW, Bell MP, McKean DJ, Abraham RT. Regulatory effects of transforming growth factor-beta on IL-2- and IL-4-dependent T cell-cycle progression.. J Immunol 1990 Mar 1;144(5):1767-76.
                    pubmed: 2407783
                  26. Nelson BJ, Ralph P, Green SJ, Nacy CA. Differential susceptibility of activated macrophage cytotoxic effector reactions to the suppressive effects of transforming growth factor-beta 1.. J Immunol 1991 Mar 15;146(6):1849-57.
                    pubmed: 1900875
                  27. Wira CR, Roche MA, Rossoll RM. Antigen presentation by vaginal cells: role of TGFbeta as a mediator of estradiol inhibition of antigen presentation.. Endocrinology 2002 Aug;143(8):2872-9.
                    pubmed: 12130550doi: 10.1210/endo.143.8.8938google scholar: lookup
                  28. Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon?. Immunol Today 1993 Jul;14(7):353-6.
                    pubmed: 8363725doi: 10.1016/0167-5699(93)90235-dgoogle scholar: lookup
                  29. Hunt JS, Roby KF. Implantation factors.. Clin Obstet Gynecol 1994 Sep;37(3):635-45.
                    pubmed: 7955650doi: 10.1097/00003081-199409000-00017google scholar: lookup
                  30. Croy BA, Esadeg S, Chantakru S, van den Heuvel M, Paffaro VA, He H, Black GP, Ashkar AA, Kiso Y, Zhang J. Update on pathways regulating the activation of uterine Natural Killer cells, their interactions with decidual spiral arteries and homing of their precursors to the uterus.. J Reprod Immunol 2003 Aug;59(2):175-91.
                    pubmed: 12896821doi: 10.1016/s0165-0378(03)00046-9google scholar: lookup
                  31. Chaouat G, Ledee-bataille N, Zourbas S, Dubanchet S, Sandra O, Martal J, Ostojojic S, Frydman R. Implantation: can immunological parameters of implantation failure be of interest for pre-eclampsia?. J Reprod Immunol 2003 Aug;59(2):205-17.
                    pubmed: 12896823doi: 10.1016/s0165-0378(03)00048-2google scholar: lookup
                  32. Nambo Y, Nagaoka K, Tanaka Y, Nagamine N, Shinbo H, Nagata S, Yoshihara T, Watanabe G, Groome NP, Taya K. Mechanisms responsible for increase in circulating inhibin levels at the time of ovulation in mares.. Theriogenology 2002 Apr 1;57(6):1707-17.
                    pubmed: 12035980doi: 10.1016/s0093-691x(02)00683-0google scholar: lookup
                  33. Kikuchi M, Nakano Y, Nambo Y, Haneda S, Matsui M, Miyake Y, Macleod JN, Nagaoka K, Imakawa K. Production of calcium maintenance factor Stanniocalcin-1 (STC1) by the equine endometrium during the early pregnant period.. J Reprod Dev 2011 Apr;57(2):203-11.
                    pubmed: 21139325doi: 10.1262/jrd.10-079kgoogle scholar: lookup
                  34. Sakurai T, Sakamoto A, Muroi Y, Bai H, Nagaoka K, Tamura K, Takahashi T, Hashizume K, Sakatani M, Takahashi M, Godkin JD, Imakawa K. Induction of endogenous interferon tau gene transcription by CDX2 and high acetylation in bovine nontrophoblast cells.. Biol Reprod 2009 Jun;80(6):1223-31.
                    pubmed: 19211809doi: 10.1095/biolreprod.108.073916google scholar: lookup
                  35. Piuko K, Bravo IG, Müller M. Identification and characterization of equine granzyme B.. Vet Immunol Immunopathol 2007 Aug 15;118(3-4):239-51.
                    pubmed: 17604123doi: 10.1016/j.vetimm.2007.05.002google scholar: lookup
                  36. Meadows SK, Eriksson M, Barber A, Sentman CL. Human NK cell IFN-gamma production is regulated by endogenous TGF-beta.. Int Immunopharmacol 2006 Jun;6(6):1020-8.
                    pubmed: 16644489doi: 10.1016/j.intimp.2006.01.013google scholar: lookup
                  37. Andrew DP, Ruffing N, Kim CH, Miao W, Heath H, Li Y, Murphy K, Campbell JJ, Butcher EC, Wu L. C-C chemokine receptor 4 expression defines a major subset of circulating nonintestinal memory T cells of both Th1 and Th2 potential.. J Immunol 2001 Jan 1;166(1):103-11.
                    pubmed: 11123282doi: 10.4049/jimmunol.166.1.103google scholar: lookup

                  Citations

                  This article has been cited 5 times.
                  1. Antczak DF, Allen WRT. Placentation in Equids. Adv Anat Embryol Cell Biol 2021;234:91-128.
                    doi: 10.1007/978-3-030-77360-1_6pubmed: 34694479google scholar: lookup
                  2. Klohonatz KM, Coleman SJ, Cameron AD, Hess AM, Reed KJ, Canovas A, Medrano JF, Islas-Trejo AD, Kalbfleisch T, Bouma GJ, Bruemmer JE. Non-Coding RNA Sequencing of Equine Endometrium During Maternal Recognition of Pregnancy. Genes (Basel) 2019 Oct 18;10(10).
                    doi: 10.3390/genes10100821pubmed: 31635328google scholar: lookup
                  3. Lee SH, Shin DJ, Kim Y, Kim CJ, Lee JJ, Yoon MS, Uong TNT, Yu D, Jung JY, Cho D, Jung BG, Kim SK, Suh GH. Comparison of Phenotypic and Functional Characteristics Between Canine Non-B, Non-T Natural Killer Lymphocytes and CD3(+)CD5(dim)CD21(-) Cytotoxic Large Granular Lymphocytes. Front Immunol 2018;9:841.
                    doi: 10.3389/fimmu.2018.00841pubmed: 29755462google scholar: lookup
                  4. Smits K, Willems S, Van Steendam K, Van De Velde M, De Lange V, Ververs C, Roels K, Govaere J, Van Nieuwerburgh F, Peelman L, Deforce D, Van Soom A. Proteins involved in embryo-maternal interaction around the signalling of maternal recognition of pregnancy in the horse. Sci Rep 2018 Mar 27;8(1):5249.
                    doi: 10.1038/s41598-018-23537-6pubmed: 29588480google scholar: lookup
                  5. Tachibana Y, Sakurai T, Bai H, Shiota K, Nambo Y, Nagaoka K, Imakawa K. RNA-seq analysis of equine conceptus transcripts during embryo fixation and capsule disappearance. PLoS One 2014;9(12):e114414.
                    doi: 10.1371/journal.pone.0114414pubmed: 25514169google scholar: lookup
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