The horse as a natural model to study reproductive aging-induced aneuploidy and weakened centromeric cohesion in oocytes.
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.
['Rizzo|Marilena|M|', 'du Preez|Nikola|N|', 'Ducheyne|Kaatje D|KD|', 'Deelen|Claudia|C|', 'Beitsma|Mabel M|MM|', 'Stout|Tom A E|TAE|', 'de Ruijter-Villani|Marta|M|']
D000375:Aging D000782:Aneuploidy D000818:Animals D018797:Cell Cycle Proteins D002503:Centromere D002868:Chromosomal Proteins, Non-Histone D005260:Female D018507:Gene Expression Regulation, Developmental D006736:Horses D059471:In Vitro Oocyte Maturation Techniques D023421:Models, Animal D009865:Oocytes D060728:Reproductive Health
aneuploidy cohesion oocyte mare aging