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
Researcher Affiliations
- College of Veterinary Medicine, Baker Institute for Animal Health, Cornell University, Ithaca, New York 14853, USA.
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.
References
This article includes 37 references
- Adams AP, Antczak DF. Ectopic transplantation of equine invasive trophoblast.. Biol Reprod 2001 Mar;64(3):753-63.
- Adams AP, Oriol JG, Campbell RE, Oppenheim YC, Allen WR, Antczak DF. The effect of skin allografting on the equine endometrial cup reaction.. Theriogenology 2007 Jul 15;68(2):237-47.
- Allen WR. The immunological measurement of pregnant mare serum gonadotrophin.. J Endocrinol 1969 Apr;43(4):593-8.
- Allen WR, Moor RM. The origin of the equine endometrial cups. I. Production of PMSG by fetal trophoblast cells.. J Reprod Fertil 1972 May;29(2):313-6.
- Allen WR, Short RV. Interspecific and extraspecific pregnancies in equids: anything goes.. J Hered 1997 Sep-Oct;88(5):384-92.
- Aluvihare VR, Kallikourdis M, Betz AG. Regulatory T cells mediate maternal tolerance to the fetus.. Nat Immunol 2004 Mar;5(3):266-71.
- Asa CS, Goldfoot DA, Garcia MC, Ginther OJ. The effect of estradiol and progesterone on the sexual behavior of ovariectomized mares.. Physiol Behav 1984 Nov;33(5):681-6.
- Billington WD. The invasiveness of transplanted mouse trophoblast and the influence of immunological factors.. J Reprod Fertil 1965 Dec;10(3):343-52.
- Borland R, Loke YW, Oldershaw PJ. Sex difference in trophoblast behaviour on transplantation.. Nature 1970 Nov 7;228(5271):572.
- Cole LA. New discoveries on the biology and detection of human chorionic gonadotropin.. Reprod Biol Endocrinol 2009 Jan 26;7:8.
- Croy BA, Rossant J, Clark DA. Recruitment of cytotoxic cells by ectopic grafts of xenogeneic, but not allogeneic, trophoblast.. Transplantation 1984 Jan;37(1):84-90.
- Daels PF, Albrecht BA, Mohammed HO. Equine chorionic gonadotropin regulates luteal steroidogenesis in pregnant mares.. Biol Reprod 1998 Nov;59(5):1062-8.
- de Mestre AM, Bacon SJ, Costa CC, Leadbeater JC, Noronha LE, Stewart F, Antczak DF. Modeling trophoblast differentiation using equine chorionic girdle vesicles.. Placenta 2008 Feb;29(2):158-69.
- de Mestre AM, Miller D, Roberson MS, Liford J, Chizmar LC, McLaughlin KE, Antczak DF. Glial cells missing homologue 1 is induced in differentiating equine chorionic girdle trophoblast cells.. Biol Reprod 2009 Feb;80(2):227-34.
- de Mestre A, Noronha L, Wagner B, Antczak DF. Split immunological tolerance to trophoblast.. Int J Dev Biol 2010;54(2-3):445-55.
- Dinger JE, Noiles EE, Bates MJ. Ovarian activity in progesterone treated mares following administration of pregnant mare serum gonadotropin.. Theriogenology 1982 Mar;17(3):305-11.
- Epple-Farmer J, Debeb BG, Smithies O, Binas B. Gender-dependent survival of allogeneic trophoblast stem cells in liver.. Cell Transplant 2009;18(7):769-76.
- Erlebacher A, Lukens AK, Glimcher LH. Intrinsic susceptibility of mouse trophoblasts to natural killer cell-mediated attack in vivo.. Proc Natl Acad Sci U S A 2002 Dec 24;99(26):16940-5.
- Flaminio MJ, Antczak DF. Inhibition of lymphocyte proliferation and activation: a mechanism used by equine invasive trophoblast to escape the maternal immune response.. Placenta 2005 Feb-Mar;26(2-3):148-59.
- Fraccaroli L, Alfieri J, Larocca L, Calafat M, Mor G, Leirós CP, Ramhorst R. A potential tolerogenic immune mechanism in a trophoblast cell line through the activation of chemokine-induced T cell death and regulatory T cell modulation.. Hum Reprod 2009 Jan;24(1):166-75.
- Huppertz B. The anatomy of the normal placenta.. J Clin Pathol 2008 Dec;61(12):1296-302.
- Kibschull M, Nassiry M, Dunk C, Gellhaus A, Quinn JA, Rossant J, Lye SJ, Winterhager E. Connexin31-deficient trophoblast stem cells: a model to analyze the role of gap junction communication in mouse placental development.. Dev Biol 2004 Sep 1;273(1):63-75.
- Lafferty KJ, Cooley MA, Woolnough J, Walker KZ. Thyroid allograft immunogenicity is reduced after a period in organ culture.. Science 1975 Apr 18;188(4185):259-61.
- McKinnon A, Carnevale EM. Ultrasonography. Equine Reproduction 1993:211–220.
- Moffett A, Loke C. Immunology of placentation in eutherian mammals.. Nat Rev Immunol 2006 Aug;6(8):584-94.
- Noronha LE, Antczak DF. Maternal immune responses to trophoblast: the contribution of the horse to pregnancy immunology.. Am J Reprod Immunol 2010 Oct;64(4):231-44.
- Oriol JG, Donaldson WL, Dougherty DA, Antczak DF. Molecules of the early equine trophoblast.. J Reprod Fertil Suppl 1991;44:455-62.
- Reimers TJ, Lamb SV, Bartlett SA, Matamoros RA, Cowan RG, Engle JS. Effects of hemolysis and storage on quantification of hormones in blood samples from dogs, cattle, and horses.. Am J Vet Res 1991 Jul;52(7):1075-80.
- Robertson SA, Sharkey DJ. The role of semen in induction of maternal immune tolerance to pregnancy.. Semin Immunol 2001 Aug;13(4):243-54.
- Roser JF, Evans JW. Luteal luteinizing hormone receptors during the postovulatory period in the mare.. Biol Reprod 1983 Sep;29(2):499-510.
- Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers.. Methods Mol Biol 2000;132:365-86.
- Seavey MM, Mosmann TR. Immunoregulation of fetal and anti-paternal immune responses.. Immunol Res 2008;40(2):97-113.
- Stewart F, Allen WR. The binding of FSH, LH and PMSG to equine gonadal tissues.. J Reprod Fertil Suppl 1979;(27):431-40.
- Tafuri A, Alferink J, Möller P, Hämmerling GJ, Arnold B. T cell awareness of paternal alloantigens during pregnancy.. Science 1995 Oct 27;270(5236):630-3.
- Trowsdale J, Betz AG. Mother's little helpers: mechanisms of maternal-fetal tolerance.. Nat Immunol 2006 Mar;7(3):241-6.
- Wallner B, Piumi F, Brem G, Müller M, Achmann R. Isolation of Y chromosome-specific microsatellites in the horse and cross-species amplification in the genus Equus.. J Hered 2004 Mar-Apr;95(2):158-64.
- Watson ED, Colston M, Broadley C. LH and progesterone concentrations during diestrus in the mare and the effect of hCG. Theriogenology 1995;43:1325–1337.
Citations
This article has been cited 5 times.- Antczak DF, Allen WRT. Placentation in Equids. Adv Anat Embryol Cell Biol 2021;234:91-128.
- 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.
- 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.
- 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.
- 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.
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