Expert Q & A

New Study Explores Genetics of Pregnancy Loss in Mares

By Adam Marcus

Chromosomal abnormalities appear to cause as many as 60% of early pregnancy losses in horses, new research shows.

An estimated 5% to 10% of equine pregnancies terminate within 70 days of the start of gestation. The study, which appears in the Equine Veterinary Journal, sheds light on some of the more common genetic problems that can disrupt gestation.

The researchers collected tissue specimens from 78 cases of early, spontaneously lost pregnancies provided by equine veterinarians in the United States, the United Kingdom, Ireland and Argentina. They conducted morphological and DNA analyses of placental and fetal tissue, genotyping 73 cases using the GGP Equine 70K SNP array and EquCab 3.0 as the reference genome, they reported.

Conclusive results were obtained in 64 of the cases, and aneuploidy was involved in 59% of those, according to the researchers. The most common anomaly (25%) was triploidy—in which the cells of the fetus have 3 copies of each chromosome rather than the usual 2—followed by trisomy (22%), marked by the presence of an extra copy of a single chromosome.

The researchers had access to 20 anembryonic vesicles—sacs that form around a fertilized egg that implants in the uterus but does not form an embryo—and 8 of those were found to have aneuploidy.
The gestational ages of early lost pregnancies with evidence of aneuploidy were short, lasting a mean of 42 days (7 weeks; range, 14-68 days). The condition was observed in embryos from all methods of impregnation: natural, intracytoplasmic sperm injection, artificial insemination and embryo transfer.

For more on the study, The Modern Equine Vet spoke with 2 researchers, Joséphine Marchand, DVM, an equine intern at Utrecht University in The Netherlands, who won the HBLB Clinical Research Prize for the presentation at British Equine Veterinary Congress in September 2025; and Amanda de Mestre, BVSc (hons) PhD, PGCAP, MRCVS, director of the Baker Institute for Animal Health, director of Cornell Equine, and the Dorothy Havemeyer McConville Professor of Equine Medicine at Cornell College of Veterinary Medicine, in Ithaca, N.Y.

MEV: This study was a follow-up of previous work looking at horses from a more discrete region. Did anything surprise you when you zoomed out a bit? How distinct are the gene pools of horses in different countries/regions, and might that make a difference in rates of these sorts of chromosomal anomalies?

Dr. Marchand: Our previous study examined early embryonic losses in Thoroughbred mares in the UK and Ireland. In this population of mares, we found over 50% of early pregnancy losses could be attributed to an abnormal number of chromosomes. We wanted to determine if the finding could be repeated in a wider population of breeding mares.

While recent studies found that Thoroughbred gene pools are relatively consistent between geographical regions, some disease causing alleles are found in vastly different frequencies in different Thoroughbred populations. Additionally, genetic variations among breeds can lead to breed-specific conditions. Further, Thoroughbreds are unique in adhering to natural mating policies, while other breeds commonly use assisted reproductive technologies such as artificial insemination and embryo transfer. Therefore, we were particularly interested in studying how the prevalence of chromosome errors might vary across a more diverse population that differed in breeding methods, breeds and geographical locations.

Interestingly, chromosomal errors in equine pregnancy loss conceptuses appear to be a common phenomenon, regardless of breed or geographical region. This study is ongoing, and the sample size is small, but data obtained to date suggest differences in the types of chromosomal anomalies that occur among the different breeding methods.

We see more of a condition called triploidy, where the embryo inherits 3 sets of chromosomes, in natural mating and Thoroughbreds. We see more single-chromosome errors, such as trisomies, across the 3 different assisted-reproductive technologies we assessed. However, the overall prevalence does not appear to differ among breeding methods or breeds. We are screening another 30 early pregnancy losses and looking forward to reporting the final findings in 2026.

MEV: Looking ahead, how much will gene-editing technologies like CRISPR (clustered regularly interspaced short palindromic repeats) obviate these kinds of anomalies? Or are they too expensive to consider?

Dr. de Mestre: The types of errors we found occur at the level of the whole chromosome or even whole genome. Therefore, for the moment, they cannot be directly repaired using techniques such as CRISPR. We do though have other genetic studies in the laboratory that aim to understand the underlying genetic basis of these errors. That means we are looking for single-nucleotide mutations in genes that control the separation of chromosomes and the stability of the genome. Down the track, these could be a target for interventions either through applying the results to make mating choices or embryo manipulations.

MEV: How might these findings be helpful to equine veterinarians? What, if anything, can they take away that could be actionable in practice?

Dr. Marchand: Equine veterinarians involved in mare management and breeding commonly encounter cases of early embryonic loss in mares. Among pregnant mares that are scanned around 14 days after breeding, about 5% to 10% will have lost the embryo by 40 days of gestation.

Sometimes, equine veterinarians can already recognize signs of a failing pregnancy on earlier scans, and they face the difficult decision of whether to terminate the pregnancy or to try supporting it with medication (such as altrenogest), only to eventually lose it anyway. These early pregnancy losses often cause significant emotional distress for both the owner and the veterinarian as the underlying reason for the loss was often not known; equine veterinarians tend to be deeply committed to their clients.

Now that we know that in more than 50% of cases these early pregnancy losses are caused by genetic abnormalities, rather than by anything the veterinarian or the owner could have done differently, it provides some reassurance. It also allows equine veterinarians to communicate with more confidence to their clients that sometimes it may be better not to use treatments such as progesterone, let the pregnancy go, and choose to breed the mare again, ensuring the breeding season is not lost.

MEV: Do you have additional studies planned to follow up on this analysis?

Dr. de Mestre: We are in the second year of a 2-year grant funded by the Grayson-Jockey Club Research Foundation. We have been collecting data on a number of potential factors that may increase or decrease the risk for chromosome errors occurring. In addition to breed and breeding method, these include exposures extending from inherent factors, such as the age of the mare and stallion, or medications they have received around the time of conception.

Once we have collected all these data, we will perform what is called a risk factor study to determine which exposures increase or decrease the chance of an embryo having an incorrect number of chromosomes. We hope this provides key factors that veterinarians and horse owners can use to guide clinical decisions or farm management decisions that reduce the chance of this condition occurring.

In the second part of this study, we are performing additional analysis to determine the origins of the errors. By that, we mean if the loss or gain of chromosomes comes from the sire or dam, and if the error occurred during meiosis, at fertilization or during the first cell divisions once the embryo forms.

We are also working with Cornell colleagues, Dr. Runi Das and Anna McKane, who are funded by the Zweig Memorial Fund, to lead a study to understand the role different-sized centromeres play in the development of these chromosomal errors. MeV