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Proceedings of the National Academy of Sciences of the United States of America2024; 121(33); e2405636121; doi: 10.1073/pnas.2405636121

Naturally occurring horse model of miscarriage reveals temporal relationship between chromosomal aberration type and point of lethality.

Abstract: Chromosomal abnormalities are a common cause of human miscarriage but rarely reported in any other species. As a result, there are currently inadequate animal models available to study this condition. Horses present one potential model since mares receive intense gynecological care. This allowed us to investigate the prevalence of chromosomal copy number aberrations in 256 products of conception (POC) in a naturally occurring model of pregnancy loss (PL). Triploidy (three haploid sets of chromosomes) was the most common aberration, found in 42% of POCs following PL over the embryonic period. Over the same period, trisomies and monosomies were identified in 11.6% of POCs and subchromosomal aberrations in 4.2%. Whole and subchromosomal aberrations involved 17 autosomes, with chromosomes 3, 4, and 20 having the highest number of aberrations. Triploid fetuses had clear gross developmental anomalies of the brain. Collectively, data demonstrate that alterations in chromosome number contribute to PL similarly in women and mares, with triploidy the dominant ploidy type over the key period of organogenesis. These findings, along with highly conserved synteny between human and horse chromosomes, similar gestation lengths, and the shared single greatest risk for PL being advancing maternal age, provide strong evidence for the first animal model to truly recapitulate many key features of human miscarriage arising due to chromosomal aberrations, with shared benefits for humans and equids.
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Publication Date: 2024-08-05 PubMed ID: 39102548PubMed Central: PMC11331123DOI: 10.1073/pnas.2405636121Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study examines chromosomal abnormalities in horse miscarriages to explore the horse as a natural animal model for understanding human miscarriage caused by chromosomal aberrations.
  • The researchers analyzed pregnancy losses in horses, identifying specific chromosomal changes and their relationship to the timing and severity of fetal lethality, highlighting similarities to human miscarriage.

Background and Importance

  • Chromosomal abnormalities are a leading cause of miscarriage in humans but are rarely documented in other species, limiting the ability to study these conditions in animal models.
  • Horses (mares) are considered a potential model because they receive detailed veterinary care during pregnancy, allowing for precise observation and collection of pregnancy loss samples.
  • The study leverages the naturally occurring pregnancy loss in horses to investigate chromosomal aberrations in products of conception (POCs) collected over the embryonic development period.

Methods and Sample

  • The study analyzed 256 POCs from mares experiencing pregnancy loss during early embryonic stages.
  • They used genetic techniques to identify chromosomal copy number aberrations, including triploidy, trisomies, monosomies, and subchromosomal changes.

Key Findings on Chromosomal Aberrations

  • Triploidy, which means having three copies of each chromosome set instead of the normal two, was the most prevalent abnormality, found in 42% of the POCs.
  • Other aberrations detected included trisomies and monosomies in 11.6% and subchromosomal abnormalities in 4.2% of POCs.
  • The aberrations involved 17 different autosomes (non-sex chromosomes), with chromosomes 3, 4, and 20 frequently affected.
  • Triploid fetuses exhibited significant developmental issues, particularly noticeable brain anomalies.

Biological and Comparative Significance

  • The pattern of chromosomal abnormalities causing pregnancy loss in horses closely mirrors that seen in humans, particularly the dominance of triploidy during organ development phases.
  • Horses and humans share highly conserved synteny—a similarity in chromosome structure and gene content—between their genomes, enhancing the validity of the horse as a model species.
  • Gestational lengths and risk factors, notably advancing maternal age being the greatest shared risk for miscarriage, align between the two species.

Conclusions and Implications

  • These findings position the horse as the first natural animal model that accurately replicates key features of human miscarriage related to chromosomal aberrations.
  • This model can help in understanding the timing and nature of chromosomal abnormalities leading to pregnancy loss.
  • Research benefits include improved insight into miscarriage causes for humans and horses alike, important for veterinary care and reproductive health management.

Cite This Article

APA
Lawson JM, Salem SE, Miller D, Kahler A, van den Boer WJ, Shilton CA, Sever T, Mouncey RR, Ward J, Hampshire DJ, Foote AK, Bryan JS, Juras R, Pynn OD, Davis BW, Bellone RR, Raudsepp T, de Mestre AM. (2024). Naturally occurring horse model of miscarriage reveals temporal relationship between chromosomal aberration type and point of lethality. Proc Natl Acad Sci U S A, 121(33), e2405636121. https://doi.org/10.1073/pnas.2405636121

Publication

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
NlmUniqueID: 7505876
Country: United States
Language: English
Volume: 121
Issue: 33
Pages: e2405636121
PII: e2405636121

Researcher Affiliations

Lawson, Jessica M
  • Department of Pathobiology and Population Sciences, Royal Veterinary College, London AL9 7TA, UK.
Salem, Shebl E
  • Department of Biomedical Sciences, Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853.
Miller, Donald
  • Department of Biomedical Sciences, Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853.
Kahler, Anne
  • Department of Pathobiology and Population Sciences, Royal Veterinary College, London AL9 7TA, UK.
van den Boer, Wilhelmina J
  • Department of Biomedical Sciences, Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853.
Shilton, Charlotte A
  • Department of Pathobiology and Population Sciences, Royal Veterinary College, London AL9 7TA, UK.
Sever, Tia
  • Department of Biomedical Sciences, Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853.
Mouncey, Rebecca R
  • Department of Pathobiology and Population Sciences, Royal Veterinary College, London AL9 7TA, UK.
Ward, Jenna
  • Department of Biomedical Sciences, Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853.
Hampshire, Daniel J
  • Department of Pathobiology and Population Sciences, Royal Veterinary College, London AL9 7TA, UK.
Foote, Alastair K
  • Rossdales Laboratories, Rossdales Ltd, Beaufort Cottages Stables, Newmarket CB8 8JS, UK.
Bryan, Jill S
  • Rossdales Laboratories, Rossdales Ltd, Beaufort Cottages Stables, Newmarket CB8 8JS, UK.
Juras, Rytis
  • Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843.
Pynn, Oliver D
  • Rossdales Veterinary Surgeons, Rossdales Ltd, Beaufort Cottages Stables, Newmarket CB8 8JS, UK.
Davis, Brian W
  • Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843.
Bellone, Rebecca R
  • Department of Population Health and Reproduction, Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95617.
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95617.
Raudsepp, Terje
  • Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843.
de Mestre, Amanda M
  • Department of Biomedical Sciences, Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853.

MeSH Terms

  • Animals
  • Horses
  • Female
  • Chromosome Aberrations
  • Abortion, Spontaneous / genetics
  • Pregnancy
  • Disease Models, Animal
  • Humans
  • Triploidy

Grant Funding

  • SPrj046 / Horserace Betting Levy Board (HBLB)
  • TBA2019 / Thoroughbred Breeders Association

Conflict of Interest Statement

Competing interests statement:The authors declare no competing interest.

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Citations

This article has been cited 3 times.
  1. Picchetta L, Ottolini CS, Tao X, Zhan Y, Jobanputra V, Vallejo CM, Mulas F, Paraboschi EM, Escribá Pérez MJ, Molinaro T, Whitehead C, Gill P, Mounts E, Babariya D, Rienzi LF, Ubaldi FM, Garcia-Velasco JA, Pellicer A, Carmi S, Hoffmann ER, Capalbo A. Maternal age and genome-wide failure of meiotic recombination are associated with triploid conceptions in humans. Am J Hum Genet 2025 Nov 6;112(11):2665-2678.
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  2. Ryan CA, Berry DP, Bugno-Poniewierska M, Burke MK, Raudsepp T, Egan S, Doyle JL. Two Cases of Chromosome 27 Trisomy in Horses Detected Using Illumina BeadChip Genotyping. Animals (Basel) 2025 Jun 22;15(13).
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