Molecular Human Reproduction, Vol 4, 281-288, Copyright © 1998 by Oxford University Press
JJ Tarin, FJ Vendrell, J Ten and A Cano
This study aims (i) to ascertain whether oxidative-stress-induced
disturbances in chromosomal distribution in the metaphase-II spindle of
mouse oocytes can be counteracted by supplementing culture medium with
antioxidants; and (ii) to determine whether supplemental intake of
antioxidants neutralizes the disturbing effects of maternal ageing on
segregation of chromosomes during the first meiotic division and
distribution of chromosomes in the metaphase-II spindle. (i): Germinal
vesicle oocytes from unstimulated 10-12 week old mice were matured in vitro
in the presence or absence of diamide and/or dithiothreitol. Metaphase-II
oocytes were fixed and stained with 4',6-diamidino-2- phenylindole (DAPI)
to detect abnormalities in chromosomal distribution. The percentage of
oocytes arrested in metaphase I (12.9% vs 28.4%; P < or = 0.05) or with
a telophase-I chromosome configuration (0.0% vs 8.2%; P < or = 0.0005)
was decreased in diamide-DTT-treated oocytes when compared to
diamide-treated oocytes. (ii): Mice were fed, from the first day of weaning
until their death, a diet supplemented or not with an antioxidant mixture
of vitamin C and vitamin E. Ovulated oocytes were fixed and stained with
DAPI or C-banded for chromosome analysis. The percentage of abnormal
(chromosome scattering and nulloploidy) or asynchronous (anaphase I or
telophase I) oocytes was 2.7-fold higher in controls than in females fed an
antioxidant diet (24.4% vs 8.9%, P < or = 0.05). Furthermore, the
percentage of aneuploidy (2.2% vs 0.0%; P < or = 0.01) and diploidy
(5.8% vs 1.7%; P < or = 0.05) was significantly higher in controls than
in females fed an antioxidant diet. These findings support Tarin's
oxidative stress hypothesis of aneuploidy and have clinical implications
for preventing both laboratory-induced and maternal-age-associated
aneuploidy in human beings.
JOURNAL ARTICLE
Antioxidant therapy counteracts the disturbing effects of diamide and maternal ageing on meiotic division and chromosomal segregation in mouse oocytes
Department of Paediatrics, Obstetrics and Gynaecology, Faculty of Medicine, University of Valencia, Spain.
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