ANTI-FERTILITY EFFECTS OF 6-CHLORO-6-DEOXY-GLUCOSE IN THE MALE-RAT

Male rats were treated with daily oral doses of 12, 24, or 48 mg/kg of 6-chloro-6-deoxy-glucose (6CDG) or with 5 mg/kg of α-chlorohydrin for 28 days. Continuous fertility trials were conducted throughout the dosing period and for 3 weeks following dosing. 12 mg/kg/day of 6CDG produced partial infertility, while 24 and 48 mg produced almost complete infertility after 7 days of dosing. Although the males continued to mate with female rats after this time, only 4 to 20% of mated females became pregnant. In addition, those females which did become pregnant carried a significantly decreased number of fetuses at sacrifice one week after the breeding period. Males dosed with 5 mg/kg/day of α-chlorohydrin showed a gradual decrease in fertility over the four-week dosing period with a significant decrease in fetal numbers observed following one week of dosing. Recovery of normal fertility was achieved after one week withdrawal from all doses of 6CDG or from α-chlorohydrin. The ATP content of spermatozoa obtained from the treated rats and measured following an in vitro incubation was significantly lower than controls for all groups at 4 weeks of dosing. However, 3 weeks following cessation of treatment, ATP had returned to control levels. The action of 6CDG is rapid in onset and associated with no effect on testis or accessory organ weight. These observations, together with the suppression of intracellular levels of ATP in epididymal spermatozoa, are consistent with an epididymal site of action of this compound or metabolites mediated through the glycolytic pathway. © 1979.