Griseofulvin-induced aneuploidy and meiotic delay in mouse oocytes: effect of dose and harvest time

Abstract

The in vivo mouse oocyte assay provides a useful system for studying both structural and numerical cytogenetic abnormalities induced by chemicals in mammalian germ cells. As part of the development of this assay for investigating chemically-induced numerical chromosome changes, the experimental and biological variables that can influence the outcome of the assay are being determined. In this study, we investigated the effect of griseofulvin (GF) administered by oral gavage on the induction of meiotic delay as measured by ovulated metaphase I (MI) oocytes and the induction of aneuploidy in metaphase II (MII) oocytes. The results indicate that GE significantly increased the frequencies of oocytes blocked in MI and of hyperploid MII oocytes compared to controls. The biological fate of delayed MI oocytes was investigated by harvesting oocytes at different times post treatment. With increasing harvest times, the frequency of MI oocytes decreased and, unexpectedly, the frequency of hyperploid MII oocytes also decreased. This suggests that some MI oocytes can overcome the GF-induced meiotic block, form a normal meiotic spindle, and progress to metaphase II as normal MII oocytes. The significance of these findings for the design and interpretation of in vivo mouse oocyte studies is discussed.