Paul Mellon Laboratory of Equine Reproduction

Newmarket, United Kingdom

Paul Mellon Laboratory of Equine Reproduction

Newmarket, United Kingdom
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De Mestre A.M.,Cornell University | De Mestre A.M.,Royal Veterinary College | Hanlon D.,Matamata Veterinary Services | Adams A.P.,Cornell University | And 7 more authors.
Reproduction | Year: 2011

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. © 2011 Society for Reproduction and Fertility.


Wilsher S.,Paul Mellon Laboratory of Equine Reproduction | Gower S.,Paul Mellon Laboratory of Equine Reproduction | Allen W.R.,Paul Mellon Laboratory of Equine Reproduction
Reproduction, Fertility and Development | Year: 2013

A polyclonal human mucin-1 (MUC1) antibody was used to stain immunohistochemically for the presence of MUC1 on the endometrium and fetal membranes in mares between 20 and 309 days of gestation. Western blot analysis demonstrated the presence of a protein equivalent in size to a human MUC1 isoform, MUC1/Y, in equine endometrium, allantochorion and amnion. At all stages of gestation examined immunoreactivity to the MUC1 antibody was detected on the apical surface of the lumenal epithelium of the endometrium and the epithelium lining the mouths and apical regions of the endometrial glands. Furthermore, it persisted unchanged on the surface of the lumenal epithelium lying beneath the highly-invasive chorionic girdle component of the trophoblast before, during and after development of the endometrial cups. The MUC1 immunoreactive protein was also present on the trophoblast and other components of the fetal membranes during the post-fixation, pre-attachment period of gestation (20-40 days) and it persisted on the apical surface of the non-invasive trophoblast of the allantochorion before, during and after attachment, microvillous interdigitation and development of the microcotyledonary epitheliochorial placenta. Hence, the delayed placentation response in mares appears to occur independently of the persistence of an immunoreactive MUC1 protein at the feto-maternal interface. © CSIRO 2013.


Wilsher S.,Paul Mellon Laboratory of Equine Reproduction | Wilsher S.,Equine Fertility Unit | Clutton-Brock A.,Paul Mellon Laboratory of Equine Reproduction | Clutton-Brock A.,Equine Fertility Unit | And 2 more authors.
Reproduction | Year: 2010

A total of 78 day 10 horse embryos were transferred non-surgically to recipient mares that had ovulated 9, 7, 6, 5, 4, 3, 2 or 1 day after (negative asynchrony), on the same day (synchronous), or 2 or 4 days before (positive asynchrony) the donor (n=6 or 8 mares per group). Pregnancy rates between 100% (6/6) and 63% (5/8) were seen in recipient mares that were between +2 and -6 days asynchronous. Embryo survival to the heartbeat stage declined in recipients that were -7 days asynchronous and no embryos survived in recipients that were -9 days asynchronous. Irrespective of uterine asynchrony, cessation of embryo mobility and fixation at the base of a uterine horn occurred when the conceptus was ∼17 days old. Conceptus growth and development was slowed when embryos were placed in negatively asynchronous uteri. At the greatest degree of negative asynchrony at which embryos survived to the heartbeat stage, i.e. -7 and -6 days, development of the embryo proper and allantois was retarded. Luteostasis was achieved in recipient mares when day 10 embryoswere transferred to recipient mares at any stage of asynchrony between -9 and +2 days with respect to the donor. These results indicate that in the horse, there is a wide window for establishment of pregnancy following embryo transfer to asynchronous recipients. Although progesterone priming of the uterus to a stage equivalent to that of the transferred embryo does not appear to be a prerequisite for embryo survival, it does nonetheless influence embryonic development. © 2010 Society for Reproduction and Fertility.

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