Chemically induced aneuploidy in female germ cells

Abstract

Female mice were dosed with the spindle poisons colcemid (5 mg/kg) or colchicine (2 mg/kg) or with a dihydropyridazinone (ICI 109,081; 5 mg/kg; which inhibits oocyte maturation) or with saline, the vehicle control. The dosed females (whose ovulation was synchronized using exogenous gonadotrophins) were mated with undosed males, 12 or 3 h prior to ovulation, coresponding to MI or MII stages in preovulatory oocytes. First-cleavage embryos derived from these matings were then analysed for numerical chromosome aberrations. There were no numerical aberrations in the embryos derived from control matings. Polyploid embryos were isolated from females dosed with colchicine. When females were dosed 3 h prior to ovulation (PO) 26% of the first-cleavage embryos were polyploid; in those dosed 12 h PO it was 100%. Colcemid and ICI 109,081 induced both polyploid and aneuploid embryos; with colcemid these aberrations were only observed in the embryos derived from oocytes of females dosed 3 h PO. At this sample time 4% of the embryos were polyploid and 24% were aneuploid. In contrast, the majority of aberrations induced by ICI 109,081 were observed in females dosed 12 h PO where 10% of the embryos were polyploid and 3% were aneuploid.