A study of horses, which share many important similarities with humans in their chromosomes and pregnancies, found that 42% of miscarriages in the first two months of pregnancy were due to complications from an extra set of chromosomes, a condition called triploidy.
“During that embryonic period [up to eight weeks from conception]”Triploidy has rarely been described in mammals outside of women,” said Mandi de Mestre, a professor of equine medicine at Cornell University. “The study tells us that during the first six weeks of gestation, this will likely be the leading cause of pregnancy loss after natural conception.”
De Mestre is the corresponding author of “Naturally occurring spontaneous abortion model in horses reveals a temporal relationship between the type of chromosomal aberration and the point of lethality,” published in Proceedings of the National Academy of Sciences.
Human miscarriages occur in 10-20% of pregnancies and are commonly associated with chromosomal errors, but suitable animal models that truly reproduce the characteristics of the condition have not been found. The new research findings will help veterinarians better understand the causes of pregnancy loss in horses and identify horses as an excellent model for studying human miscarriages.
“We were able to study the impact of chromosomal errors throughout the entire pregnancy in the mare,” said de Mestre. “We found that triploidy is only associated with losses in the early stages of pregnancy.”
In the study, de Mestre’s lab at Cornell, and formerly at the Royal Veterinary College in London, received 256 samples of fetuses and placenta from veterinarians who treated horses with failed pregnancies over a 10-year period. Using the samples, the researchers were able to investigate the prevalence of different types of chromosomal copy number errors associated with pregnancy loss. They found that chromosomal errors occurred in 57.9% of pregnancy losses up to day 55 of gestation, in 57.2% of losses between days 56 and 110, and in only 1.4% of losses between days 111 and the end of pregnancy. Aneuploidy (loss or gain of a single, complete chromosome) was associated primarily with miscarriages in the first 10 weeks of pregnancy, while deletions or duplications of only part of a chromosome were found in miscarriages after 110 days. These findings turned out to be remarkably similar to those seen in several large-scale studies conducted in women, according to the paper.
Horses are a good model for studying human pregnancies because they have a similar gestation period (11 months versus nine months for women) and the embryo develops at a similar rate in the early stages. In addition, horse chromosomes have a very similar genetic content to human chromosomes, making them especially relevant for the study of chromosomal errors.
The causes of miscarriages in women in the early stages of pregnancy have been difficult to determine because most fetuses during this period are lost at home, leaving scientists with no material (or data) to study. The study’s findings provide insight into the frequency of chromosomal errors during the period equivalent to the first six weeks of human gestation.
Because of the value of horses and the emotional attachment their owners have to them, horses receive a high level of care, with routine monitoring of pregnancies, which then provide extensive data for research.
Other animal models, such as mice, are not comparable to human pregnancies. Mice have a gestation period of approximately three weeks and natural pregnancy losses in mice are low.
In terms of equine health, the study provides new details about common chromosomal abnormalities that will likely change the clinical management of pregnancies. For example, if a clinician determines that a horse has a major chromosomal error, he or she may no longer choose to prolong the pregnancy by administering hormones, a common practice in pregnant mares. The study will also direct researchers toward developing new diagnostic tests for chromosomal abnormalities in horse fetuses and investigating the molecular mechanisms that lead to these abnormalities.
“This research has provided a foundation for understanding the genetic causes of pregnancy loss in horses, often referred to as pregnancy loss of unknown cause,” said Shebl Salem, a postdoctoral researcher in de Mestre’s Equine Pregnancy Laboratory and co-lead author of the study.
Other co-lead authors include Jessica Lawson of the Royal Veterinary College in London, UK, and Donald Miller, manager of Mestre’s lab.
The study was funded in part by the Horseracing Betting Tax Board and the Thoroughbred Breeders Association.