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

Marilena Rizzo, Nikola du Preez, Kaatje D Ducheyne, Claudia Deelen, Mabel M Beitsma, Tom A E Stout, Marta de Ruijter-Villani

Research output: Contribution to journalArticleAcademicpeer-review

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 in vitro. Oocytes from aged mares showed reduced gene expression for the centromere cohesion stabilizing protein, Shugoshin 1. Moreover, in vitro 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.

Original languageEnglish
Pages (from-to)22220-22232
Number of pages13
JournalAging
Volume12
Issue number21
DOIs
Publication statusPublished - 15 Nov 2020

Keywords

  • oocyte
  • aging
  • aneuploidy
  • cohesion
  • mare

Fingerprint

Dive into the research topics of 'The horse as a natural model to study reproductive aging-induced aneuploidy and weakened centromeric cohesion in oocytes'. Together they form a unique fingerprint.

Cite this