Collaborative study shows mares may be a valuable model for studying miscarriage in humans
A recently published study led by Dr. Mandi de Mestre, from Cornell University, revealed that horses may be a valuable model species for studying miscarriage in humans. The UC Davis Veterinary Genetics Laboratory (VGL) was honored to collaborate on that work.
In humans, one in six recognized pregnancies ends in miscarriage, the majority of which are caused by an abnormal number or structure of chromosomes. The most common chromosomal abnormality is aneuploidy, where an embryo has extra or missing chromosome(s) (normal number for humans is 46 - or 23 pairs, two copies of each). Interestingly, similar chromosomal issues in pregnancy loss tissue are rarely reported in other mammals.
In 2020, Dr. de Mestre published the first evidence of aneuploidy as a cause of early pregnancy loss in mares, leading researchers to further investigate this phenomenon in horses. The recently published study used advanced genomic techniques to determine the frequency of chromosomal abnormalities in early equine pregnancy loss by examining equine conceptuses from early naturally occurring failed pregnancies and placental and fetal tissue from pregnancy losses occurring after 110 days of gestation.
A total of 256 products of conception from 244 mares were analyzed. The findings revealed that chromosomal abnormalities were present in more than half of the pregnancy losses occurring before 110 days of gestation, with triploidy (3 copies of each chromosome) being the most common abnormality found (42.1%) in conceptuses from pregnancy losses before 55 days of gestation. Testing at the VGL, using short tandem repeat markers (STR), identified and/or confirmed three alleles for the markers tested confirming that there were three copies of the chromosome in which these markers reside.
We are lucky to collaborate with Dr. de Mestre on several genetic studies in horses, including this one, and our genetic testing services allowed us to help Dr. de Mestre’s team confirm that having three copies of every chromosome is a common cause of early pregnancy loss in the mare”. –Dr. Rebecca Bellone, VGL director and co-author of this study.
In addition, findings support that abnormalities of equine chromosome 20 were the most frequently detected, followed by chromosomes 3 and 4. These chromosomes are syntenic (with similar gene location and distribution) to human chromosomes 16, 4, and 7, which are the most frequent chromosomal abnormalities seen in humans. This suggests that there may be some type of characteristic of these chromosomes that increases their instability, resulting in early pregnancy loss.
Dr. Mandi de Mestre, Dorothy Havemeyer McConville Professor at Baker Institute for Animal Health, Cornell University, and senior author of this study, states
This work has helped us to explain the underlying cause of a large proportion of clinical cases of early pregnancy loss in horses thanks to collaborations with veterinarians and colleagues at the VGL. It also demonstrates that the rates of chromosomal abnormalities in equine pregnancy losses are remarkably similar to those seen in human studies. This will allow us to use a comparative approach to further advance knowledge for horses and humans.”
Given these similarities and the similar gestation length (10-11 months), the mare represents a unique model organism experiencing natural miscarriages that are more frequent with advanced maternal age. Better understanding of chromosomal abnormalities and their role in equine pregnancy losses may provide valuable insight into human miscarriages.
To read the full study, visit https://doi.org/10.1073/pnas.2405636121