By Victoria Lindsay

Researchers at the Royal Veterinary College (RVC) and Texas A&M University have found that aneuploidies, which are the gain or loss of a whole chromosome (similar to Down’s syndrome in humans), cause a significant proportion of equine pregnancies to fail within the first two months of pregnancy. This could turn out to be one of the most common causes of early pregnancy loss in the mare, as it is in humans. 

“Early pregnancy loss remains a very frustrating condition for clinicians to treat as the underlying cause is unknown in around 80% of cases,” said research leader Dr Mandi de Mestre, Reader in Reproductive Immunology at the RVC. Between 5 and 10% of equine pregnancies are lost in in the first 8 weeks despite best efforts of breeders, and this proportion has also been consistent over a number of generations. This represents a large financial loss to the equine industry across various disciplines. Identifying causes of early pregnancy loss is vital to improving outcomes for mares and their breeders, and to improving breeding programmes. 

RVC researchers collaborated with seven veterinary practices to collect samples from 55 naturally occurring pregnancy losses from across the UK and Ireland and used three different genetic methods (whole genome sequencing, genotyping array and digital droplet PCR) to identify and confirm the presence of the aneuploidies in lost pregnancies that were not present in controls.  

“Despite early pregnancy loss being a large issue in a number of species, we actually know relatively little about the direct causes,” said RVC PhD researcher Charlotte Shilton, “This can be frustrating for both human couples and those involved in animal breeding programs as we currently can’t offer much of an explanation or ways to prevent it. This research, inspired by progress made in human medicine, is the first step in identifying genetic causes of pregnancy losses that may one day allow owners and veterinarians to make more informed breeding decisions.” 

Researchers found that 20% of equine early pregnancy losses were aneuploid, contrasting with previous reports of aneuploidies in liveborn horses being very rare. This mirrors human pregnancies, where aneuploid foetuses usually die early in development. This study identified several aneuploidies in chromosomes that had never had a reported aneuploidy in horses previously, indicating that these are lethal to the foetus. This is supported by the fact that very few aneuploidies across various mammalian species are carried to term. 

“These findings will allow researchers to develop new diagnostic tests for pregnancy losses, which would offer hope to thousands of owners of breeding mares that suffer this condition,” said Dr de Mestre. 

This project was funded by the Thoroughbred Breeders’ Association. 

Shilton, C.A., Kahler, A., Davis, B.W. et al. Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse. Nature (Scientific Reports) 10, 13314 (2020). https://doi.org/10.1038/s41598-020-69967-z 

Victoria Lindsay, Royal Veterinary College PhD Student 

Victoria has been a member of the BSAS Early Careers Council for two years and is in the final year of her PhD at the Royal Veterinary College studying the genetic architecture of exertional rhabdomyolysis in horses.