TBA Veterinary Update - ongoing commitment to veterinary research
The Thoroughbred Breeders’ Association (TBA) and Horserace Betting Levy Board (HBLB) are pleased to confirm continued financial support of veterinary research for the benefit of the thoroughbred breeding industry. Following Prof. Mandi de Mestre’s (Cornell University) earlier work looking into causative factors of pregnancy loss in thoroughbred broodmares (click here to view a presentation by Mandi at the TBA's 2022 AGM), the TBA is delighted that Mandi now leads two new studies exploring both foetal and neonatal health. The scholarship will investigate musculoskeletal disorders in newborn foals, in close collaboration with Prof. Kristien Verheyen (RVC), Dr. Liam MacGillivray (NEH) and Orlagh O’Reilly (PhD student). Whilst the large project will examine foetal health in the pregnant mare, in partnership with Prof. Madeleine Campbell and Prof. Richard Lea (both at Nottingham University).
- Epidemiology and Genetics of Congenital Musculoskeletal Disorders in Neonatal Thoroughbreds, Prof. Mandi de Mestre, Prof. Kristien Verheyen, Dr. Liam MacGillivray and Orlagh O’Reilly
Status
This four-year project officially commenced on 1 February 2023, with the appointment of a PhD student, Orlagh O’Reilly.
Background
Aside from routine neonatal health checks, conformational abnormalities that are present from birth are the most common reason a veterinary surgeon is asked to evaluate a foal in the first 48 hours of life, which can cause concern and additional expense for breeders. Flexural (FLD) and angular limb deformities (ALD) are examples of conditions that occur commonly throughout the thoroughbred population and require remedial farriery, sometimes veterinary intervention and potentially surgery. If they are not addressed promptly these deviations may progress, depending on severity, to inhibit the foal’s ability to stand, suckle and function healthily, or to negatively impact their welfare, conformation, movement, sales price/commercial value and the athletic potential of each individual. The mortality rate of foals with severe congenital deformities remains quite high, regardless of improvements in stud management practices and veterinary treatments over the last 20 years.
Objectives
The origin and cause of these limb deformities are thought to be multifactorial and are currently poorly understood. This study aims to investigate if exposures around the time of ovulation and during pregnancy modulate the risk of conformational abnormalities. These findings will then be extremely beneficial as they will inform stud and veterinary management techniques, which could alter the incidence of these conformational abnormalities, thereby creating a positive impact on welfare, soundness and performance and leading to a reduction in mortality rates relative to the more extreme cases. As a consequence, this may decrease foaling complications, dystocia numbers and improve broodmare fertility and reproductive health.
The study also aims to understand how genetic variants (changes in the genome) can lead to the development of congenital musculoskeletal disorders. If and once identified, genetic variants could then assist in supporting the development of a diagnostic tool that could guide breeders in selecting mating combinations that might improve the chance of avoiding severe limb deformities.
The research team would welcome enquiries from any stud farms interested in participating in the research this season or next season – please contact Orlagh O’Reilly on [email protected] for further information.
- Development of a non-invasive diagnostic test to assess foetal health in the pregnant mare, Prof. Mandi de Mestre (Cornell University), Prof. Madeleine Campbell and Prof. Richard Lea (both at Nottingham University).
Status
It is hoped that a research assistant (to be based at Nottingham University) will be appointed by 1 June 2023.
Background
Whilst equine conception rates have improved significantly over the last 15 years, the rate of pregnancy loss has changed little, with 10-15% of confirmed Thoroughbred pregnancies lost before or at parturition. The underlying cause of the pregnancy loss is often not identified. The Royal Veterinary College’s Equine Pregnancy Laboratory recently described a genetic condition called aneuploidy (gain or loss of a whole chromosome) in 20% of failed early equine pregnancies (EPL), making it the most common cause of early pregnancy loss described to date. Pregnancy loss in the later stages of gestation (‘slipped’ pregnancies) and stillbirths have also been attributed to genetic characteristics incompatible with life, such as aneuploidy, and deleterious single changes in the genome sequence in genes such as procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1), associated with Fragile Foal Syndrome. These pregnancy losses of a non-infectious origin remain a significant clinical challenge for veterinary surgeons, as there are few diagnostic options available to them to accurately predict a pregnancy carrying a lethal variant, or to retrospectively diagnose one.
Objectives
A diagnostic test that identifies genetic causes of pregnancy loss in mares would represent a significant step forward in the clinical management of the pregnant mare. In women, aneuploidy is detected after 10 weeks of gestation, through the isolation of circulating cell free foetal DNA (cfDNA) from the mother’s blood, a technique known as non-invasive pre-natal testing (NIPT). In the mare, NIPT has identified cfDNA in a small number of studies, suggesting that this procedure may be a viable approach to detecting foetal aneuploidy in the pregnant mare. The aim of this HBLB/TBA funded project is to therefore develop a single non-invasive diagnostic test with the purpose of identifying mares that are carrying a pregnancy that has a lethal genetic variant such as aneuploidy, and perhaps other relevant genetic markers or abnormalities.
The diagnostic methods being investigated provide the flexibility to either diagnose genetic conditions using tissues obtained following a pregnancy loss, or to predict them in pregnant mares using a non-invasive blood test that detects foetal DNA in the dam’s blood. It is currently unknown at what timing following conception the accurate detection of equine cfDNA may be possible, but it is currently believed that this is unlikely to be before endometrial cup formation, i.e. 35 days. Depending on timing, this information may then be used by the veterinary surgeon to target treatments for mares both at risk of pregnancy loss, or, alternatively, to add useful diagnostic information in the days and weeks after they have suffered a pregnancy loss. The project will also explore the ethical and legal framework for applying such testing in equine veterinary practice, to ensure that it is performed in the best interests of all stakeholders.
As part of this study, the research team at Nottingham University will be offering free health screening of high-risk pregnant mares. Stud farms interested in participating in this project are encouraged to contact Prof. Mandi de Mestre on [email protected] or Prof. Richard Lea on [email protected] for further details.
The TBA wishes to thank all breeders who have made a donation to the TBA foal levy (collected during the foal registration process with the General Stud Book administered by Weatherbys). This money is ringfenced specifically for veterinary research projects and along with industry funding, enables the TBA to support this hugely valuable work.