Postovulatory ageing of mouse oocytes in vivo and premature centromere separation and aneuploidy

Abstract

Two paramount observations exist regarding aneuploidy in human oocytes: its association with maternal age and its more frequent occurrence during meiosis I. Numerous experimental studies have shown that fertilization of postovulatory aged oocytes is coupled with reproductive failure and cytogenetic aberrations in embryos. However, the basic cytogenetic defect(s) of aged oocytes that causes these abnormalities has not been adequately described. The objective of this study was to test the hypothesis that postovulatory oocyte ageing results in increased frequencies of premature centromere separation (PCS) in metaphase II (MII) oocytes and aneuploidy in zygotes. MII oocytes and one-cell zygotes were collected from superovulated mice at different times after ovulation and fertilization. Chromosomes were C-banded and analyzed for structural and numerical aberrations. The frequencies of PCS in oocytes significantly (p < 0.01) increased with time postovulation: 15 h (15 of 529, 2.8%), 20 h (82 of 627, 13.1%), and 25 h (118 of 502, 23.5%). In zygotes, the frequencies of hyperploidy significantly (p < 0.01) increased with time post-fertilization: 0-4 h (0 of 260), 4-8 h (5 of 212, 2.4%), and 8-12 h (8 of 262, 3.1%). These data support the hypothesis that postovulatory ageing results in elevated levels of PCS in oocytes and of aneuploidy in zygotes. The link between PCS and aneuploidy may be random segregation of sister chromatids during anaphase II.