Genetics of early placental development and early pregnancy loss

Funded by the Thoroughbred Breeders Association, United Kingdom

Early pregnancy loss (EPL) occurs in 7-10% of Thoroughbred (TB) pregnancies making it one of the most significant contributors to reproductive wastage in the United Kingdom’s TB industry. Despite the considerable economic losses associated with this condition, the cause of EPL is identified in less than 25 % of cases. Human studies show genetic causes account for between 40-90% of first trimester losses in women, however, the importance and implications of genetic changes in early equine pregnancy remain unknown.

Recent investigations in the laboratory have, for the first time, identified a method to isolate and culture placental cells from failed pregnancies. Preliminary investigations on 12 of these pregnancies identified 83 areas along the chromosome showing variations in the amount of genetic material when compared to normal adult thoroughbreds. Of these regions, 17 had never before been identified as areas of genetic variation in TBs. The aim of the current project is to investigate genetic causes of EPL. Normal genetic changes occurring throughout placental development will be identified and these findings used as a basis to identify genetic abnormalities in failed pregnancies. Blood samples from mares and sires together with an analysis of pedigrees will help to identify a hereditary component to EPL. Finally, analysis of specific areas of the genome will be carried out to determine if specific abnormalities or variations may render the pregnancy susceptible to viral invasion, in particular Equine Herpes Virus (EHV) which we have shown to be present in placental tissue from early pregnancies. The contribution of EHV to failure of equine pregnancy in the early stages is unknown but it is well recognised as a cause of equine abortion in later stages of pregnancy. The combined results of this study may enable the development of genetic tests to be used as diagnostic tools to determine the cause of EPL. Additionally, determination of the hereditary aspects of this condition may allow the prediction of the risk of EPL with certain mating combinations potentially allowing breeders to more accurately select mare/sire crosses to reduce the risk of pregnancy failure. By investigating novel causes of EPL this study will provide valuable information to enhance our knowledge of the condition which is essential if we are to reduce its prevalence and the associated economic and management implications.

The first findings from this project can be found in Scientific Reports via this open access link https://www.nature.com/articles/s41598-020-69967-z

4 year grant funded by the Alborada Trust PhD student Jessica Roach BVetMed MRCVS

Approximately 5-10% of pregnancies result in abortion or stillbirth making these losses a significant contributor to reproductive wastage in Thoroughbreds. The most common reported reason for abortion and stillbirths in the last extensive review published in the UK (2003) was twisting of the umbilical cord and long cords (38.8% of all abortions/stillbirths). Despite the high incidence of this condition in the UK, there is very little up to date research as to the risk factors, pathological characteristics or inheritance of overly long or twisted umbilical cords. The aim of this project is to explore and define these fields as well as providing an update on the incidence of this common cause of abortion, thereby informing the industry on the best way to tackle this issue and work towards minimising losses resulting from umbilical cord pathologies.

A project funded by the HBLB and the Racing Foundation lead by Professor Kristien Verheyen and her co-workers Dr Mandi De Mestre, Professor Renate Weller, Dr Shebl Salem and PhD student Rebecca Mouncey.

There are currently no up-to-date figures on the extent to which Thoroughbreds are being lost from the industry prior to entering race training. Data from over 20 years ago suggested that of all foals born only around 50% entered training. Of these only 60% started a race as a 2-year-old, with only 5% of these runners winning enough prize money to cover their training fees (Wilsher et al. 2006). Clearly, these figures suggest significant economic losses for the industry. No UK studies have investigated risk factors for horses being prematurely lost from the industry.

There is substantial evidence from human studies that early life experiences, including in utero, have important consequences on musculoskeletal health and disease in adulthood. It is well established in humans that exercise during growth is beneficial for bone development and that these beneficial effects may prevent fractures in later life.

Several studies in horses have shown that development of musculoskeletal tissues is influenced by early exercise (Barneveld and van Weeren 1999, Firth et al. 2011). However, there is no information on whether or how early exercise affects injury risk and/or performance in later life. 

The objectives of this project are therefore to:    

• Describe and quantify the causes of young Thoroughbreds being lost from the industry prior to entering race training     Identify risk factors associated with these early losses    
• Describe management practices, including exercise regimens, implemented on stud farms for foals, weanlings, and yearlings, including preparation for sales    
• Identify the association between management practices and musculoskeletal disease or injury prior to entering race training    
• Identify associations between early exercise prior to entering race training and musculoskeletal injury during 2- and 3-year-old race training and racing performance.  

We are seeking to recruit a birth cohort of around 700 foals born in the 2018/19 season. We plan to monitor them from birth until the end of their 3rd year of life (and hopefully beyond!), regularly collecting data on how they are managed throughout their early life stages and whilst in training, with a special focus on orthopaedic issues. We will also gather information from veterinary and farriery records, to establish reasons for early losses, types of injuries or diseases incurred, and veterinary interventions and treatments. The data will then be collated and analysed to quantify and identify risk factors for early losses, injury and performance.

We envisage that the findings from this project can be used to:

1.    Reduce early loss of horses from the industry prior to entering training

2.    Increase retention of young horses in training

3.    Optimise musculoskeletal development

4.    Reduce musculoskeletal injury and optimise performance  

Ultimately leading to improved economic performance and significant welfare benefits to the Thoroughbred racing industry  

References

Barneveld A, van Weeren PR (1999) Conclusions regarding the influence of exercise on the development of the equine musculoskeletal system with special reference to osteochondrosis. Equine Vet J Suppl. (31):112-9.  

Firth EC, Rogers CW, van Weeren PR, Barneveld A, McIlwraith CW, Kawcak CE, Goodship AE, Smith RK (2011) Mild exercise early in life produces changes in bone size and strength but not density in proximal phalangeal, third metacarpal and third carpal bones of foals. Vet J. 190(3):383-9.  

Wilsher S, Allen WR, Wood JL (2006) Factors associated with failure of thoroughbred horses to train and race. Equine Vet J. 38(2):113-8.