The overall goal of Mandi's research program is to identify key mechanisms that permit normal growth and survival of the fetus and pathologies that interfer with this process. Her current research focuses on two aspects of pregnancy: (i) the mechanisms that regulate the development of the placenta in normal healthy pregnancies, (ii) identification and characterisation of causes of pregnancy failure. Her studies, which are primarily in the horse, address fundamental questions that aim to result in the development of novel therapies to treat and clincially manage conditions of equine pregnancy and infertility (e.g. abortion). One of the hormones of pregnancy her group studies, Chorionic gonadotropin, is produced by the placenta of both horses and humans during pregnancy, but not by most other species used experimentally. This means that results gained from their studies in the horse may also be valuable beyond equine health to provide new knowledge relevant and applicable to human reproduction.  

Currently Mandi's funded research projects fall into these areas; i) Genetics of early pregnancy loss in Thoroughbreds (funded by Thoroughbred Breeders Association), (ii) Unravelling genetic and environmental contributions to abortions associated with umbilical pathologies (funded by Alborada Trust), (iii) Development of software for managing breeding mares (Concept Development Fund, RVC), (iv) collaboration with Professor Kristien Verheyen, Does early life experience affect injury risk and performance in later life (HBLB), (v) collaboration with Dr Suzannah Williams and Lindsay Baxter, University of Oxford, Age-related changes in oocyte quality and implications for early pregnancy failure using a horse model (Wellcome TRust Clinician PhD studentship to Dr Lindsay Baxter). 

Shilton, CA; Kahler, A; Crabtree, JR; Crowhurst, J; Davis, BW; McGladdery, AJ; Wathes, DC; Raudsepp, T; de Mestre, AM
Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse
Scientific Reports, 10, Article number: 13314 (2020) 

AM de Mestre, BV Rose, YM Chang, DC Wathes, KLP Verheyen. Multivariable analysis to determine risk factors associated with early pregnancy loss in thoroughbred broodmares, Theriogenology, 2018

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 Jul 10. pii: REP-18-0270. doi: 10.1530/REP-18-0270

Jordan E Read, Victoria Cabrera-Sharp, Phoebe Kitscha, Judith E Cartwright, Peter J King, Rob C Fowkes and Amanda M de Mestre. Glial Cells Missing 1 regulates equine Chorionic Gonadotrophin beta subunit via binding to the proximal promoter. Front. Endocrinology, 26 April 2018, 9: 195 https://doi.org/10.3389/fendo.2018.00195

Timpson, A; de Mestre, AM; Elliott, J; Harris, PA; Cheng, Z; Mirczuk, S M; Callan, L; Rainbow, L; Menzies-Gow, NJ.
Seasonal and dietary influences on adipose tissue and systemic gene expression in control and previously laminitic ponies.
Journal of Equine Veterinary Science, 2018

ROSE BV, FIRTH M, MORRIS B, ROACH JM, WATHES DC, VERHEYEN KLP, DE MESTRE AM.Descriptive study of current therapeutic practices, clinical reproductive findings and incidence of pregnancy loss in intensively managed thoroughbred mares. Anim Reprod Sci. 2018 Jan;188:74-84. doi: 10.1016/j.anireprosci.2017.11.011.

CAMPBELL MLH, HAMPSHIRE D, HAMSTEAD L, ROSE B, SMITH KC, DE MESTRE AM The effects of intrauterine infusion of peanut oil on endometrial health, salivary cortisol and interovulatory period in mares. Theriogenology, 2017 Oct 15;102:116-125. doi: 10.1016/j.theriogenology.2017.07.009. Epub 2017 Jul 13.

ALEKSIC D, BLASCHKE L, MIßBACH S, HÄNSKE J, WEIß W, HANDLER J, ZIMMERMANN W, CABRERA-SHARP V, READ JE, DE MESTRE AM, O'RIORDAN R, MOORE T, KAMMERER R. Convergent evolution of pregnancy-specific glycoproteins in the human and horse. Reproduction. 2016 Jun 8.

CARNEY K, CHANG YM, WILSON S, CALNAN C, REDDY PS, CHAN WY, GILMARTIN T, HERNANDEZ G, SCHAFFER L, HEAD SR, MORLEY J, DE MESTRE AM, AFFLECK K, GARDEN OA. Regulatory T-cell-intrinsic amphiregulin is dispensable for suppressive function. J Allergy Clin Immunol. 2016 Jun;137(6):1907-9.

B.V. ROSE, V. CABRERA-SHARP, M.J. FIRTH, F.E. BARRELET, S. BATE, I.J. CAMERON, J.R. CRABTREE, J. CROWHURST, A.J. MCGLADDERY, H. NEAL, J. PYNN, O.D. PYNN, C. SMITH, Z. WISE, K.L.P. VERHEYEN, D.C. WATHES, A.M. DE MESTRE A method for isolating and culturing placental cells from failed early equine pregnancies. Placenta, Volume 38, February 2016, Pages 107–111

CABRERA-SHARP V, READ JE, RICHARDSON S, KOWALSKI AA, ANTCZAK DF, CARTWRIGHT JE, MUKHERJEE A, DE MESTRE AM. SMAD1/5 signaling in the early equine placenta regulates trophoblast differentiation and chorionic gonadotropin secretion. Endocrinology. 2014 Aug;155(8):3054-64

ROSE, B., FIRTH, M., MORRIS, B., NICHOLSON, C., VERHEYEN, K., WATHES, D.C. AND DE MESTRE, A.M. (2014), Incidence and Risk Factors Associated with Early Pregnancy Loss in Thoroughbreds. Equine Veterinary Journal, 46: 16. doi: 10.1111/evj.12323_35

ACKERMAN WE 4TH, CARTER AM, DE MESTRE AM, GOLOS TG, JESCHKE U, KUSAKABE K, LAURENT LC, PARAST MM, ROBERTS RM, ROBINSON JM, RUTHERFORD J, SOMA H, TAKIZAWA T, UI-TEI K, LASH GE. IFPA Meeting 2012 Workshop Report I: comparative placentation and animal models, advanced techniques in placental histopathology, human pluripotent stem cells as a model for trophoblast differentiation. Placenta. 2013 Mar;34 Suppl:S3-5

ANTCZAK, DF, DE MESTRE, AM, WILSHER S AND ALLEN WR. The Equine Endometrial Cup Reaction: A Feto-maternal Signal of Significance. Annual Review of Animal Biosciences, 2013, Vol. 1419

DE MESTRE A. Reproductive failure in horses: identifying the problem. Vet Rec. 2013 Jan 12;172(2):42

NORONHA, L. E., HUGGLER, K. E., DE MESTRE, A. M., MILLER, D. C. AND ANTCZAK, D. F. (2012). Molecular evidence for natural killer-like cells in equine endometrial cups. Placenta. 33(5):379-86. PubMed ID 22357194

CRABTREE, J.R., CHANG, Y., AND, DE MESTRE A.M. (2012). Clinical presentation, treatment and possible causes of persistent endometrial cups illustrated by two cases. Equine Veterinary Education. 24(5):251-259.

ACKERMAN WE 4TH, BULMER JN, CARTER AM, CHAILLET JR, CHAMLEY L, CHEN CP, CHUONG EB, COLEMAN SJ, COLLET GP, CROY BA, DE MESTRE AM, DICKINSON H, DUCRAY J, ENDERS AC, FOGARTY NM, GAUSTER M, GOLOS T, HAIDER S, HEAZELL AE, HOLLAND OJ, HUPPERTZ B, HUSEBEKK A, JOHN RM, JOHNSEN GM, JONES CJ, KALIONIS B, KÖNIG J, LORENZON AR, MOFFETT A, MOREIRA DE MELLO JC, NUZZO AM, PARHAM P, PAROLINI O, PETROFF MG, PIDOUX G, RAMÍREZ-PINILLA MP, ROBINSON WP, ROLFO A, SADOVSKY Y, SOMA H, SOUTHCOMBE JH, TILBURGS T, LASH GE. (2012). IFPA Meeting 2011 workshop report III: Placental immunology; epigenetic and microRNA-dependent gene regulation; comparative placentation; trophoblast differentiation; stem cells. Placenta. 33 Suppl:S15-22. PubMed ID 22154501

DE MESTRE A.M., HANLON D., ADAMS, A.P., RUNCAN E., LEADBEATER J.C., ERB H., COSTA C., MILLER D., ALLEN W.R., ANTCZAK,D.F. (2011). Functions Of Ectopically Transplanted Invasive Horse Trophoblast. Reproduction. 141(6):849-56. Faculty of 1000 selection PubMed ID 21389079

ROBBIN M.G., WAGNER B., NORONHA L.E., ANTCZAK D.F. AND DE MESTRE A.M. (2011). Subpopulations of equine blood lymphocyte expressing regulatory T cell markers. Vet Immunol Immunopathol 140:90-101 PubMed ID 21208665

DE MESTRE AM., ANTCZAK, DF., AND ALLEN, WR. (2010). 'Equine Chorionic Gonadotropin' in Equine Reproduction, 2nd edition, A. McKinnon, E Squires, W. Vaala, D. Varner, Blackwell Publishing

DE MESTRE, A.M., NORONHA, L.E., WAGNER, B., AND ANTCZAK, D.F. (2010). Split immunological tolerance to trophoblast. Int. J. Dev. Biol. 54(2-3):445-55. PubMed ID 19876828

DE MESTRE, A.M., MILLER, D., ROBERSON, MS., LIFORD, J., CHIZMAR, LC., MCLAUGHLIN, K.E., AND ANTCZAK, D. F. (2009). Glial cells missing homologue 1 is induced in differentiating equine chorionic girdle trophoblast cells. Biol. Reprod. 80:227-234. PubMed ID 18971425

DE MESTRE, A.M., BACON, S.J., COSTA, C.C., LEADBEATER, J.C., NORONHA, L.E., STEWART, F., AND ANTCZAK, D.F. (2008). Modeling trophoblast differentiation using equine chorionic girdle vesicles. Placenta 29:158-169. Pubmed ID 18054076

DE MESTRE, A.M., STAYKOVA, M.A., HORNBY, J.R., WILLENBORG, D.O., AND HULETT, M.D. (2007). Expression of the heparan sulfate-degrading enzyme heparanase is induced in infiltrating CD4+ T cells in experimental autoimmune encephalomyelitis and regulated at the level of transcription by early growth response gene 1. J. Leukoc. Biol. 82:1289-1300. Pubmed ID 17656651

DE MESTRE, A.M., SOE-HTWE, T., SUTCLIFFE, E.L., RAO, S., PAGLER, E.B., HORNBY, J.R., AND HULETT, M.D. (2007). Regulation of mouse heparanase gene expression in T lymphocytes and tumor cells. Immunol. Cell Biol. 85:205-214. Pubmed ID 17213834

DE MESTRE, A.M., RAO, S., HORNBY, J.R., SOE-HTWE, T., KHACHIGIAN, L.M., AND HULETT, M.D. (2005). Early growth response gene 1 (EGR1) regulates heparanase gene transcription in tumor cells. J. Biol. Chem. 280:35136-35147. PubMed ID 16093249

DE MESTRE, A.M., KHACHIGIAN, L.M., SANTIAGO, F.S., STAVKOVA, M.A., AND HULETT, M.D. (2003). Regulation of inducible heparanase gene transcription in activated T cells by early growth response 1. J. Biol. Chem. 278:50377-50385. PubMed ID 14522979

MURPHIE*, A.M., HOPMAN, T.J., SCHUG, M.D., AQUADRO, C.F., BOWLING, A.T., MURRAY, J.D., CAETANO, A.R. AND ANTCZAK, D.F. (1999). Equine dinucleotide repeat loci COR021-COR040. Anim. Genet. 30:235-237. Pubmed ID 10443004

 

Conference papers 2015-2018

de Mestre AM, BV Rose, YM Chang, DC Wathes, KLP Verheyen. Factors that modify the risk of early pregnancy loss and early conceptus growth in Thoroughbreds, International Symposium in Equine Reproduction, Cambridge UK, July 2018.

de Mestre AM. Update on pregnancy loss. ISER Veterinary and Breeders Symposium, Newmarket, July 2018. 

de Mestre, AM Update on risk factors for pregnancy loss and how to ameliorate them. BEVA Congress, September 2017,

de Mestre, AM Current broodmare management in the UK: could it be done better? BEVA Congress, September 2017

de Meste AM, ‘Early pregnancy loss – current research and the state of our knowledge’ and ‘Immunology of pregnancy and ‘Immunological aspects of early pregnancy loss’ Rossdales Pregnant Mare and Stallion Course, January 2017, Newmarket. 

JE Read, V Cabrera-Sharp, V Offord, S Mirczuk, R Fowkes, AM de Mestre. Dynamic changes in gene expression and signalling during early placental development in the horse. Fertility, Edinburgh, UK, January 2017. 

de Mestre AM, Molecular Mechanisms Regulating Early Placental Development in the Horse. Society for the Study of Reproduction, July 2016, San Diego, USA. 

de Mestre AM Molecular mechanisms regulating early equine placental development in health and disease. Society for Reproduction and Fertility, Oxford, UK. July 2015

de Meste AM . Transcriptional regulation of equine Chorionic Gonadotrophin. International Conference on Biotechnology and Welfare in Animal Husbandry Krakow, Poland, June 2015. 

de Meste AM Risk Factors associated with early pregnancy failure. British Society for Animal Science Science with Impact Annual Meeting, Chester, UK, April 2015. 

 

Mandi teaches reproductive biology on the following courses; Bvetmed1, Bvetmed2, GAB, Bvetmed5 (Module leader for equine stud medicine), and BSc3. She also supervises 4-6 undergraduate students each year on the BSc Bioveterinary Science and BVetMed course who choose to carry out projects in her laboratory either as part of the course or over the summer. Mandi has a strong interest in mentoring veterinary students in research. She was Course Director for Veterinary Team Leadership and Professionalism (VTLP) course for veterinary, nursing and bioveterinary science undergraduate students that aims to develop students leadership and teamwork skills through self awareness, social awareness and relational competence. She is Co-Leader of the Professional Orientation and Development Programme for BVM3 students. 

Mandi and her group regularly present to industry representatives, horse breeders and veterinary surgeons. Recently this has included presentations at Thoroughbred Breeders Association Breeders Day and  Horsetech 2017 and 2018.  Please get in touch if your organisation would like us to speak to your members about updates in equine reproduction.

• Early-life determinants of performance and the Economics of Thoroughbred breeding

  

  The project aims to improve understanding of the impact of Thoroughbreds’ early-life health and management on later-life racing performance and the financial viability of Thoroughbred breeding enterprises.

  Findings from the project will align with key priorities from the Thoroughbred industry’s welfare strategy. Firstly, by increasing transparency around the fate and welfare of Thoroughbreds bred for racing during their early-life stages, and secondly by informing strategies to reduce musculoskeletal disease and injury and improve industry retention and economic viability.

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• Investigation of clinical predictors of equine umbilical cord torsion and abortion

  

  Researchers at the RVC are leading a collaboration with colleagues at Cornell University, Rossdales Laboratories and Hagyard Equine Medical Institute to unravel the reason the umbilical cord twists excessively in mid-pregnancy and new ways to be able to detect the twisting prior to the pregnancy being aborted. Epidemiological modelling is being utilised to carry out evidence-based refinement of the current diagnostic criteria for UCT, allowing for more reliable comparison of distinct populations within the UK and overseas.

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• The epidemiology and genetics of congenital musculoskeletal disorders in neonatal Thoroughbreds

  

  The project aims to investigate the contributions of gestational exposures and genetic variants to the risk of congenital developmental orthopaedic disorders (cDOD) in Thoroughbred foals.

  The project will provide novel insights into the development, incidence and genetic basis of cDOD in Thoroughbred foals. The project outputs will inform evidence-based management modifications for Thoroughbred breeders to reduce the risk of cDOD in foals and improve broodmare fertility and welfare long-term. 

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