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Reproduction (Cambridge, England)2011; 141(6); 849-856; doi: 10.1530/REP-10-0462

Functions of ectopically transplanted invasive horse trophoblast.

Abstract: The invasive and fully antigenic trophoblast of the chorionic girdle portion of the equine fetal membranes has the capacity to survive and differentiate after transplantation to ectopic sites. The objectives of this study were to determine i) the survival time of ectopically transplanted allogeneic trophoblast cells in non-pregnant recipient mares, ii) whether equine chorionic gonadotropin (eCG) can be delivered systemically by transplanted chorionic girdle cells, and iii) whether eCG delivered by the transplanted cells is biologically active and can suppress behavioral signs associated with estrus. Ectopically transplanted chorionic girdle survived for up to 105 days with a mean lifespan of 75 days (95% confidence interval 55-94) and secreted sufficient eCG for the hormone to be measurable in the recipients' circulation. Immunohistochemical labeling of serial biopsies of the transplant sites and measurement of eCG profiles demonstrated that graft survival was similar to the lifespan of equine endometrial cups in normal horse pregnancy. The eCG secreted by the transplanted cells induced corpora lutea formation and sustained systemic progesterone levels in the recipient mares, effects that are also observed during pregnancy. This in turn caused suppression of estrus behavior in the recipients for up to 3 months. Thus, ectopically transplanted equine trophoblast provides an unusual example of sustained viability and function of an immunogenic transplant in a recipient with an intact immune system. This model highlights the importance of innate immunoregulatory capabilities of invasive trophoblast cells and describes a new method to deliver sustained circulating concentrations of eCG in non-pregnant mares.
Publication Date: 2011-03-09 PubMed ID: 21389079PubMed Central: PMC5181105DOI: 10.1530/REP-10-0462Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural

Summary

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This research investigates the viability and functionality of invasive horse trophoblast cells transplanted to different locations, assessing their survivability, ability to deliver systemic equine chorionic gonadotropin (eCG), and the biological activity of the eCG they produce.

Research Objective and Methodology

  • The research aimed to determine a few key aspects related to the transplantation of allogeneic trophoblast cells. The objectives were to determine the survival time of these cells when transplanted to non-pregnant mares, investigate if the transplanted cells can deliver equine chorionic gonadotropin (eCG) systemically and assess if this eCG is biologically active enough to suppress estrus behavior.
  • The researchers used immunohistochemical labeling of serial biopsies of the transplant sites and measurement of eCG profiles as part of their methodology.

Findings of the Study

  • The research found that the transplanted chorionic girdle could survive for up to 105 days with an average lifespan of 75 days. These cells were capable of secreting sufficient eCG for the hormone to be measurable in the recipient’s circulation.
  • Trophoblasts transplanted to ectopic sites showed survival rates similar to the lifespan of equine endometrial cups in a typical horse pregnancy.

Biological Activity of eCG

  • The researchers discovered that the eCG secreted by transplanted cells was biologically active, inducing corpora lutea formation and maintaining systemic progesterone levels in the recipient mares.
  • This hormonal activity was strong enough to suppress estrus behavior for about three months, similar to the effects observed during equine pregnancy.

Implications of the Research

  • This study provides an interesting case of the survival and functional behavior of an immunogenic transplant within a recipient with a functioning immune system. It also points out the importance of the inherent immunoregulatory abilities of invasive trophoblast cells.
  • The research outlines a new method for delivering ongoing circulating concentrations of eCG in non-pregnant mares using transplanted trophoblast cells.
  • These findings could have significant implications for controlling reproductive behavior and hormonal balances in mares.

Cite This Article

APA
de Mestre AM, Hanlon D, Adams AP, Runcan E, Leadbeater JC, Erb HN, Costa CC, Miller D, Allen WR, Antczak DF. (2011). Functions of ectopically transplanted invasive horse trophoblast. Reproduction, 141(6), 849-856. https://doi.org/10.1530/REP-10-0462

Publication

ISSN: 1741-7899
NlmUniqueID: 100966036
Country: England
Language: English
Volume: 141
Issue: 6
Pages: 849-856

Researcher Affiliations

de Mestre, Amanda M
  • College of Veterinary Medicine, Baker Institute for Animal Health, Cornell University, Ithaca, New York 14853, USA.
Hanlon, David
    Adams, A Paige
      Runcan, Erin
        Leadbeater, Jane C
          Erb, Hollis N
            Costa, Christina C
              Miller, Donald
                Allen, W R
                  Antczak, Douglas F

                    MeSH Terms

                    • Analysis of Variance
                    • Animals
                    • Biopsy
                    • Cell Survival
                    • Chorionic Gonadotropin / biosynthesis
                    • Chorionic Gonadotropin / blood
                    • Estrus / metabolism
                    • Female
                    • Graft Survival
                    • Horses
                    • Immunohistochemistry
                    • Sexual Behavior, Animal
                    • Time Factors
                    • Transplantation, Homologous
                    • Trophoblasts / immunology
                    • Trophoblasts / metabolism
                    • Trophoblasts / transplantation
                    • Vulva / immunology
                    • Vulva / metabolism
                    • Vulva / surgery

                    Grant Funding

                    • R01 HD049545 / NICHD NIH HHS
                    • R01-HD049545 / NICHD NIH HHS

                    Conflict of Interest Statement

                    Declarations of interest There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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                    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. Read JE, Cabrera-Sharp V, Offord V, Mirczuk SM, Allen SP, Fowkes RC, de Mestre AM. Dynamic changes in gene expression and signalling during trophoblast development in the horse. Reproduction 2018 Oct 1;156(4):313–330.
                      doi: 10.1530/REP-18-0270pubmed: 30306765google scholar: lookup
                    3. Read JE, Cabrera-Sharp V, Offord V, Mirczuk SM, Allen SP, Fowkes RC, de Mestre AM. Dynamic changes in gene expression and signalling during trophoblast development in the horse. Reproduction 2018 Oct 1;156(4):313-330.
                      doi: 10.1530/REP-18-0270pubmed: 29991567google scholar: lookup
                    4. Brosnahan MM, Silvela EJ, Crumb J, Miller DC, Erb HN, Antczak DF. Ectopic Trophoblast Allografts in the Horse Resist Destruction by Secondary Immune Responses. Biol Reprod 2016 Dec;95(6):135.
                      doi: 10.1095/biolreprod.115.137851pubmed: 27760752google scholar: lookup
                    5. Antczak DF, de Mestre AM, Wilsher S, Allen WR. The equine endometrial cup reaction: a fetomaternal signal of significance. Annu Rev Anim Biosci 2013 Jan;1:419-42.