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Biology of reproduction2002; 66(6); 1612-1620; doi: 10.1095/biolreprod66.6.1612

Control of expression of major histocompatibility complex genes in horse trophoblast.

Abstract: In most mammals, the fetus limits its presentation of paternal antigens to the mother by suppressing the cell-surface expression of proteins of the major histocompatibility complex (MHC) on trophoblast. In the horse, however, functional, polymorphic MHC class I antigens are expressed at high levels on the invasive trophoblast cells of the chorionic girdle between Days 32 and 36 of pregnancy, although not on the adjacent noninvasive trophoblast of the chorion and allantochorion membranes. In this study, the control of MHC class I gene expression was investigated in invasive and noninvasive horse trophoblast, and the MHC class I loci expressed by invasive trophoblast were identified. Northern blot hybridization of Day 33-34 conceptus tissue revealed both transcriptional and posttranscriptional regulation of cell-surface MHC class I expression in horse trophoblast. The invasive MHC class I-positive trophoblast showed levels of steady-state mRNA nearly as high as those in lymphoid tissues from adult horses, whereas noninvasive MHC class I-negative trophoblast also contained transcripts for MHC class I, but at lower levels similar to those present in adult horse nonlymphoid tissue. We also cloned and sequenced polymerase chain reaction products from the transmembrane and cytoplasmic regions of MHC class I transcripts in chorionic girdle and lymphocytes, and determined that horse invasive trophoblast appears to transcribe the same MHC class I loci transcribed in lymphocytes, including both polymorphic and nonpolymorphic loci. These data from the horse demonstrate that functional alloantigen presentation by trophoblast can be a normal part of early pregnancy.
Publication Date: 2002-05-22 PubMed ID: 12021038DOI: 10.1095/biolreprod66.6.1612Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

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The article investigates how horse trophoblast cells (cells involving in development of placenta) manage to express major histocompatibility complex (MHC) class I genes during the early stages of pregnancy. Contrary to most mammals, where fetal-paternal antigen presentation is suppressed, in horses, these antigens are actively expressed, particularly in invasive trophoblast cells.

Understanding Trophoblast’s Role and MHC Class I genes

  • Trophoblasts are cells that are pivotal in the early stages of mammalian pregnancy, being involved in implantation and placenta formation. They are notable in this study for their unique behavior in horses wherein they prominently display MHC class I gene expression.
  • The Major Histocompatibility Complex (MHC) genes play a crucial role in the immune system of mammals and the body’s ability to distinguish self from non-self. In the context of pregnancy, this typically involves shielding the fetus (which carries paternal antigens foreign to the mother’s immune system) by suppressing the display of MHC proteins on the cell surface of the trophoblasts. However, in horses, MHC class I expression is high on invasive trophoblasts, opening up opportunities for further understanding of this somewhat unconventional behavior.

Detailed Results & Experimental Methods

  • The research studied MHC class I gene expression in both invasive and noninvasive horse trophoblasts, from day 33-34 of conception, and made several critical observations. In the invasive trophoblasts, the study found mRNA levels almost at par with lymphoid tissues from adult horses. At the same time, noninvasive trophoblasts also had MHC class I transcripts, albeit at lower levels. These findings suggest at both transcriptional and post-transcriptional regulation of MHC class I expression.
  • The researchers also cloned and sequenced polymerase chain reaction products from MHC class I transcripts in order to verify which specific MHC class I loci the horse trophoblasts are transcribing. After a comparison with lymphocyte transcripts, it was found that both polymorphic and non-polymorphic loci seen in lymphocytes were transcribed by the invasive trophoblasts. This reveals more about how MHC class I gene expression is regulated in horse trophoblast cells, and suggests that the presentation of functional alloantigen by the trophoblast is actually a normal part of early horse pregnancy.

Cite This Article

APA
Bacon SJ, Ellis SA, Antczak DF. (2002). Control of expression of major histocompatibility complex genes in horse trophoblast. Biol Reprod, 66(6), 1612-1620. https://doi.org/10.1095/biolreprod66.6.1612

Publication

ISSN: 0006-3363
NlmUniqueID: 0207224
Country: United States
Language: English
Volume: 66
Issue: 6
Pages: 1612-1620

Researcher Affiliations

Bacon, S J
  • James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA. sbacon@mtholyoke.edu
Ellis, S A
    Antczak, D F

      MeSH Terms

      • Allantois / metabolism
      • Animals
      • Chorion / metabolism
      • Female
      • Gene Expression Regulation
      • Histocompatibility Antigens Class I / genetics
      • Histocompatibility Antigens Class II / genetics
      • Horses / embryology
      • Immunohistochemistry
      • Organ Specificity
      • Pregnancy
      • Transcription, Genetic
      • Trophoblasts / metabolism
      • beta 2-Microglobulin

      Grant Funding

      • HD-15974 / NICHD NIH HHS
      • HD-34086 / NICHD NIH HHS

      Citations

      This article has been cited 12 times.
      1. Rowland AL, Miller D, Berglund A, Schnabel LV, Levine GJ, Antczak DF, Watts AE. Cross-matching of allogeneic mesenchymal stromal cells eliminates recipient immune targeting. Stem Cells Transl Med 2021 May;10(5):694-710.
        doi: 10.1002/sctm.20-0435pubmed: 33369287google scholar: lookup
      2. Todd ET, Thomson PC, Hamilton NA, Ang RA, Lindgren G, Viklund Å, Eriksson S, Mikko S, Strand E, Velie BD. A genome-wide scan for candidate lethal variants in Thoroughbred horses. Sci Rep 2020 Aug 4;10(1):13153.
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      6. Rapacz-Leonard A, Dąbrowska M, Janowski T. Major histocompatibility complex I mediates immunological tolerance of the trophoblast during pregnancy and may mediate rejection during parturition. Mediators Inflamm 2014;2014:579279.
        doi: 10.1155/2014/579279pubmed: 24812442google scholar: lookup
      7. Noronha LE, Huggler KE, de Mestre AM, Miller DC, Antczak DF. Molecular evidence for natural killer-like cells in equine endometrial cups. Placenta 2012 May;33(5):379-86.
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      11. Tallmadge RL, Lear TL, Antczak DF. Genomic characterization of MHC class I genes of the horse. Immunogenetics 2005 Nov;57(10):763-74.
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      12. Silver LW, Hogg CJ, Belov K. Plethora of New Marsupial Genomes Informs Our Knowledge of Marsupial MHC Class II. Genome Biol Evol 2024 Aug 5;16(8).
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