H. Jackson, A. Jones, E. R. Cooper
Nov 1, 1969
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Journal
Journal of reproduction and fertility
Abstract
Hexamethylphosphoramide (HMPA) an industrial solvent was given to male rats of proven fertility in daily consecutive doses. Testes and epididymes and pituitary glands were studied histologically. 500 mg/kg orally rapidly induced sterility due to aspermia with no effect on libido. The compound was mildly cumulative and striking effects were produced by 3 weeks of daily oral treatment of 100 mg/kg; all animals became sterile by the sixth week and remained sterile for almost three months. 25 mg/kg daily for one month had no effect on fertility. Animals receiving 100 mg/kg showed severe damage to the testes by the end of three weeks. Testes examined 18 weeks after the treatment showed full spermatogenesis in some tubules. At 500 mg/kg daily for 5 or 6 days there were no regenerative changes in spermatogenesis after 14 weeks. Only the testes were affected by weight changes; accessory sexual organs adrenals thyroid and pituitary were within normal limits. In the 20x 100 mg/kg and 5 x 500 mg/kg groups there was enlargement of basophil cells associated with coarse granulation hyalinization and vacuolation. Oral treatment with HMPA from two commercial sources for 6 weeks at 100 mg/kg produced multiple lung abscesses. The presence of 6 methyl groups in the phosphoramide molecule is essential for antifertility action. Simple modification in the chemical structure of HMPA resulted in loss of the sterilization action.