Induced Aneugenic Effects in Mouse Oocytes In Vivo

Abstract

Aneugenic effects of the chemicals with antitumor activity were studied in mouse oocytes in vivo by cytogenetic analysis. In control mice, no oocytes with numerical chromosome aberrations were found. Colchicine (0.2-4 mg/kg), paclitaxel (2.5-7.5 mg/kg), and etoposide (10-60 mg/kg) produced a significant dose-dependent aneugenic effects (induction of up to 25% aneuploid oocytes) and increased the yield of oocytes arrested in the meiotic MI stage and with premature separation of sister chromatid. Paclitaxel induced up to 20% polyploid chromosomes. Doxorubicin (2.5 mg/kg), melphalan (10 mg/kg), and cisplatin (5-10 mg/kg) exhibited weak aneugenic activity (induction of up to 5% aneuploid oocytes). Cyclophosphamide (10-80 mg/kg) had minor effect on the studied parameters. Methotrexate (25-200 mg/kg) exhibited no aneugenic activity, but significantly increased the level of polyploid cells. The observed aneugenic effects included hypo- and hyperploidy in various proportions or hypoploidy, but no solely hyperhaploidy.

The Effect of Dietary Folic Acid Supplementation on Female Germ Cell Aneuploidy

“…A colchicine dose of 0.2 mg/kg was chosen because it had been previously shown to significantly induce aneuploidy in mouse oocytes and, in those studies, did not arrest oocytes in MI (Mailhes et al, 1988;Mailhes & Yuan, 1987b;Mailhes et al, 1990;Pligina et al, 2017;Tease & Fisher, 1986).…”

“…Colchicine has the ability to enhance aneuploidy in mammalian oocytes as reported in mice and hamsters (Hummler & Hansmann, 1985;Mailhes & Yuan, 1987b;Mailhes et al, 1990;Pligina et al, 2017;Tease & Fisher, 1986). The ability of colchicine to induce aneuploidy in oocytes depends on several variables including: route of administration, dose selection, treatment time, treatment duration before cell harvesting, and animal age (Mailhes & Marchetti, 1994a).…”

“…injection or through oral gavage (Mailhes et al, 1990). Doses of colchicine ranging from 0.1 to 6.0 mg/kg have been used to induce aneuploidy in mouse oocytes (Mailhes et al, 1988;Mailhes & Yuan, 1987b;Mailhes et al, 1990;Tease & Fisher, 1986;Pligina et al, 2017). A dose of 0.1 mg/kg colchicine administrated by i.p.…”

“…did not significantly induce aneuploidy in MII mouse oocytes (Mailhes & Yuan, 1987;Mailhes, 1988), whereas doses between 0.2 to 0.4 mg/kg induced a significant increase in aneuploidy incidence when administrated by the i.p. route (Tease & Fisher, 1986;Mailhes, 1988;Pligina et al, 2017). Colchicine doses that exceeded 2.0 mg/kg administrated via i.p.…”

“…Colchicine doses that exceeded 2.0 mg/kg administrated via i.p. injection were shown to arrest oocyte maturation and result in the production of only MI oocytes (Mailhes & Yuan, 1987;Pligina et al, 2017). However, a dose of 4.0 mg/kg was reported to significantly increase oocyte aneuploidy when administrated orally (Mailhes et al, 1990).…”