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A. W. CRAIG, B. W. FOX and H. JACKSON

Summary.

The effect of whole-body irradiation on the fertility of the male rat and mouse has been examined by systematic weekly matings of the treated animals. In both species, irradiation with 300r produces a short period of sterility associated with oligospermia. This occurs at about 45 days after treatment in the mouse and 65 days in the rat. Histological examination shows that the main effect is on the spermatogonial stages but there are obvious differences in the timing and extent of these radiation effects in the two species. The time from treatment to the onset of sterility is a measure of the overall duration of spermatogenesis. The highest dose level used, 500r, did not cause a rapid onset of sterility in contrast to the action of some alkylating agents, which rapidly induce infertility.

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H. JACKSON, B. W. FOX and A. W. CRAIG

Summary.

  1. The antifertility effects of a number of simple alkane sulphonic esters have been examined in the male rat by a combination of serial mating of treated animals and histological examination of the testes. The results are compared and contrasted with those obtained with Busulphan (Myleran), dimethylmyleran and various derivatives of ethyleneimine.
  2. A spectrum of results on various stages of spermatogenesis has been obtained, which is difficult to reconcile with a common mode of action due to alkylation of cellular materials.
  3. Certain simple esters produce strikingly different effects. Thus, methylethanesulphonate and methylmethanesulphonate cause early sterility due to interference with spermatids and spermatozoa. Isopropyl alkane sulphonates, on the other hand, cause sterility only after a delay of several weeks.
  4. These esters are effective by mouth and their action is cumulative. Methylmethanesulphonate and methylethanesulphonate in small daily doses produce predictable periods of sterility, according to the dose rate given, which are completely reversible. There is no indication of any action on libido, nor evidence so far of toxic effects from these courses of treatment.
  5. With the series of compounds examined, it has been possible to move the focus of drug action from spermatogonia to spermatids and spermatozoa with reduction of side effects. It is concluded that this work demonstrates that selective interference with fertility in the male is a distinct possibility.

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B. W. FOX, H. JACKSON, A. W. CRAIG and T. D. GLOVER

Summary.

Serial sperm counts have been made in rabbits treated with alkylating agents. After single injections of Busulphan, Tretamine and isopropyl methanesulphonate, aspermia developed during the 10th and 11th weeks. Other simple monofunctional esters of methane and ethane sulphonic acids, which induced sterility in rats as a result of their action on spermatozoa and late spermatids, did not depress the sperm count or interfere with sperm motility in the rabbit. The results suggest that the duration of spermatogenesis in the rabbit is about 10 weeks and indicate that in this species, as in rats and mice, a steady turnover of spermatozoa occurs. Fertility tests in male rabbits after administration of Tretamine showed that small doses readily induced sterility which could be maintained by continued administration.