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Home / Equine Research Bank / Aging (Albany NY) / The horse as a natural model to study reproductive aging-ind...
Aging2020; 12(21); 22220-22232; doi: 10.18632/aging.104159

The horse as a natural model to study reproductive aging-induced aneuploidy and weakened centromeric cohesion in oocytes.

Abstract: Aneuploidy of meiotic origin is a major contributor to age-related subfertility and an increased risk of miscarriage in women. Although age-related aneuploidy has been studied in rodents, the mare may be a more appropriate animal model to study reproductive aging. Similar to women, aged mares show reduced fertility and an increased incidence of early pregnancy loss; however, it is not known whether aging predisposes to aneuploidy in equine oocytes. We evaluated the effect of advanced mare age on (1) gene expression for cohesin components, (2) incidence of aneuploidy and (3) chromosome centromere cohesion (measured as the distance between sister kinetochores) in oocytes matured . Oocytes from aged mares showed reduced gene expression for the centromere cohesion stabilizing protein, Shugoshin 1. Moreover, matured oocytes from aged mares showed a higher incidence of aneuploidy and premature sister chromatid separation, and weakened centromeric cohesion. We therefore propose the mare as a valid model for studying effects of aging on centromeric cohesion; cohesion loss predisposes to disintegration of bivalents and premature separation of sister chromatids during the first meiotic division, leading to embryonic aneuploidy; this probably contributes to the reduced fertility and increased incidence of pregnancy loss observed in aged mares.
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Publication Date: 2020-11-02 PubMed ID: 33139583PubMed Central: PMC7695376DOI: 10.18632/aging.104159Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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.

The research studied reproductive aging in horses as a potential model to understand similar processes in humans. The investigation focused on age-related genetic abnormalities in egg cells, as well as a weakening in the structure that holds chromosomes together.

Introduction and Purpose

  • The study builds on the established understanding that aneuploidy (abnormally structured cells) is a significant contributor to decreased fertility and heightened risk of miscarriage in older women.
  • Previous aneuploidy studies have primarily used rodents as their subjects. However, the researchers hypothesized that mares – female horses – may be a more accurate model for studying reproductive aging; in part due to similarities between mares and women, such as a decline in fertility and increased chances of early pregnancy loss with age.
  • The research aimed to gain insights into whether aging increases the likeliness of aneuploidy in equine oocytes – the cells that give rise to an egg.
  • Three major aspects were examined: the gene expression for cohesin components, the occurrence of aneuploidy, and the cohesion of chromosome centromeres (which is a measure of how close sister kinetochores are to each other) in mature oocytes.

Methods and Findings

  • The study found that older mares had a decrease in gene expression for Shugoshin 1, a protein that stabilizes cohesion at the centromere.
  • Moreover, matured oocytes from older mares showed higher instances of aneuploidy, premature separation of sister chromatids and weakened cohesion at the centromere.

Conclusions and Implications

  • Given these findings, the study proposes the mare as a valid model for studying the effects of aging on centromeric cohesion.
  • This loss of cohesion could lead to the disintegration of paired chromosomes (bivalents) and early separation of sister chromatids during the first stage of cell division, resulting in embryonic aneuploidy.
  • Such genetic abnormalities are likely to contribute to the lessened fertility and increased rate of pregnancy loss often observed in older mares, and, by implication, in older women.

Cite This Article

APA
Rizzo M, du Preez N, Ducheyne KD, Deelen C, Beitsma MM, Stout TAE, de Ruijter-Villani M. (2020). The horse as a natural model to study reproductive aging-induced aneuploidy and weakened centromeric cohesion in oocytes. Aging (Albany NY), 12(21), 22220-22232. https://doi.org/10.18632/aging.104159

Publication

Aging
ISSN: 1945-4589
NlmUniqueID: 101508617
Country: United States
Language: English
Volume: 12
Issue: 21
Pages: 22220-22232

Researcher Affiliations

Rizzo, Marilena
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the Netherlands.
du Preez, Nikola
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the Netherlands.
Ducheyne, Kaatje D
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the Netherlands.
  • Sussex Equine Hospital, Ashington, RH20 3BB, United Kingdom.
Deelen, Claudia
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the Netherlands.
Beitsma, Mabel M
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the Netherlands.
Stout, Tom A E
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the Netherlands.
  • Department of Production Animal Studies, University of Pretoria, Pretoria, 0110, South Africa.
de Ruijter-Villani, Marta
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the Netherlands.

MeSH Terms

  • Aging / genetics
  • Aging / metabolism
  • Aging / pathology
  • Aneuploidy
  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Centromere / genetics
  • Centromere / metabolism
  • Centromere / pathology
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Horses
  • In Vitro Oocyte Maturation Techniques
  • Models, Animal
  • Oocytes / metabolism
  • Oocytes / pathology
  • Reproductive Health

Conflict of Interest Statement

The authors declare that there are no conflicts of interest that could be perceived as prejudicing the impartiality of the research reported.

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Citations

This article has been cited 5 times.
  1. Roach J, Arango Sabogal JC, Smith K, Foote A, Verheyen K, de Mestre AM. Multivariable analysis to determine risk factors associated with abortion in mares.. Reprod Fertil 2022 Nov 1;3(4):301-12.
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