The horse as a natural model to study reproductive aging-induced aneuploidy and weakened centromeric cohesion in oocytes
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Authors
Rizzo, Marilena
Du Preez, Nikola
Ducheyne, Kaatje D.
Deelen, Claudia
Beitsma, Mabel M.
Stout, T.A.E. (Tom)
De Ruijter-Villani, Marta
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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.
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Keywords
Aneuploidy, Meiosis, Age-related subfertility, Mare, Pregnancy loss, Horse (Equus caballus)
Sustainable Development Goals
Citation
Rizzo, M., Du Preez, N., Ducheyne, K.D. et al. 2020, 'The horse as a natural model to study reproductive aging-induced aneuploidy and weakened centromeric cohesion in oocytes', Aging, vol. 12, no. 21, pp. 22220-22232.