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New study reveals link between chromosomal errors and pregnancy loss in mares

equine-miscarriage-2

 Researchers from the Royal Veterinary College (RVC), as part of a team from Cornell University, have identified chromosomal errors as a common cause of pregnancy loss in mares. Whilst chromosomal abnormalities are widely acknowledged as a common cause of human miscarriage, responsible for up to 82 per cent of pregnancy loss, there have been limited reports in other species until now. Due to the similarities between human and horse chromosome structures and other pregnancy characteristics, this research supports the use of horses as a novel model organism to study miscarriage in women, particularly due to chromosomal abnormalities.


The findings of this study mean it is possible to now account for potential causes in 60-70 per cent of equine early pregnancy loss – previously this figure was only around 20-30 per cent. This can be used to help inform veterinary management of pregnancies, allowing for pregnancy losses to be screened and a diagnosis made retrospectively to provide an explanation for the loss to the owner and inform clinical treatment of a subsequent pregnancy. It also supports researchers to target the mechanisms that lead to these very common chromosomal errors which, in turn, could aid future treatments.

The study investigated the prevalence of aberrations in chromosomes in 256 cases of pregnancy loss, finding that triploidy (three haploid sets of chromosomes), was the most common aberration (42 per cent). In a healthy pregnancy, a foetus has two haploid sets, one from each parent.

Other abnormalities identified included trisomy – the presence of one extra whole chromosome – and monosomy – the loss of one whole chromosome, in almost 12 per cent of pregnancies.

The study marks a significant step forward into researchers' ability to understand how chromosomal abnormalities are linked to pregnancy loss over the embryonic period in women. Despite the link between the two being well established, there are significant barriers to enable further research. These difficulties include issues in detecting human pregnancy loss prior to week six-seven of gestation, in obtaining samples from the earliest of early pregnancy losses and the absence of comparable samples from normally progressing pregnancies. There are also significant ethical restrictions to consider hence the need to explore alternative models.

Due to the high level of gynaecological monitoring and care that mares receive, the similarities in gestation length and the pace of early embryonic development, horses present a new viable model to better understand the link between pregnancy loss and chromosomal abnormalities in humans.

The research team analysed 256 samples collected from 244 mares between 2013 and 2023, observing occurrences of the various types of chromosomal aberrations responsible for the pregnancy loss. The team behind the study was overseen by Dr Amanda de Mestre, from Cornell's Baker Institute for Animal Health and included the RVC's Dr Jessica Lawson as well as other researchers from Texas A&M University and University of California Davis. Other lead authors included Dr Shebl Salem, a postdoctoral fellow at Cornell and Mr Don Miller, laboratory manager of the Cornell Equine Pregnancy Laboratory.

Dr Jessica Lawson, Research Fellow at the Royal Veterinary College, said:

"Working with Prof. de Mestre and her team at Cornell has been an exciting opportunity. In addition to the significant findings in the early stages of the equine pregnancy we, for the first time, have identified sub-chromosomal aberrations in an aborted fetus and a stillborn foal. These aberrations likely constitute a rare but important cause of later term pregnancy loss, and we look forward to continuing to investigate the clinical significance of these genomic changes."

Mandi de Mestre Dorothy Havemeyer McConville Professor in Equine Medicine, Baker Institute for Animal Health, College of Veterinary Medicine, Cornell

"I am very grateful to the RVC for providing access to a bank of tissues generated over my time in England. This has allowed us to explore the impact of this new type of chromosomal error over the whole of pregnancy pinpointing exactly when each type of genetic error causes death of the embryo or fetus. The work was also made possible due to important contributions by our collaborating veterinary surgeons and pathologists and long-term collaborators at Texas A and M and University of California Davis who independently verified samples.

"Of course, these discoveries would not be possible without an amazing team in the Equine Pregnancy Laboratory, notably Dr Shebl Salem, Dr Jessica Lawson and Mr Don Miller and who each led different aspects of the work."

This research builds on the RVC's knowledge and expertise in equine research, where it undertakes and contributes to world leading innovation and projects in various areas of equine science and medicine. More recently, studies have explored pregnancy in Thoroughbreds, diet and disease and findings in pre-purchase examinations. Other key areas of the RVC's ongoing research includes Stem Cell Therapies, Laminitis, Equine Cushing's disease, Elastic Band Resistance and Lameness and life for racehorses post-retirement.


https://www.rvc.ac.uk/equine-vet/news/new-study-reveals-link-between-chromosomal-errors-and-pregnancy-loss-in-mares

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