Antifertility Substances and Their Assessment in the Male Rodent

Abstract

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.

Dominant lethal mutations induced in male mice by methyl methanesulphonate

“…In fertility studies in the rat (Jackson et al, 1961) maximal sensitivity was found in the second and third weeks; a single dose of 50 mg.fkg. causing sterility at this time.…”

Male fertility after VAPEC-B chemotherapy for Hodgkin's disease and non-Hodgkin's lymphoma

“…Both MOPP and MVPP were found to produce a very high incidence of azoospermia, with only a few men recovering spermatogenesis after treatment (Chapman et al, 1979;Whitehead et al, 1982). Procarbazine, a component of both regimens, causes complete aplasia of the germinal epithelium in the rat (Jackson et al, 1961) and the non-human primate (Sieber et al, 1978), and mustine and vinblastine are also implicated in the germinal epithelial damage following MOPP/MVPP (Spitz, 1948;Vilar, 1975). Of these, only vinblastine is included in the ABVD regimen, which is reported as causing no permanent gonadal damage.…”

Effect of Some Chemicals on Spermatogenesis in Rhesus Monkeys

“…A single intraperitoneal injection of Busulphan has been reported to cause reversible sterility in rats after about 9 weeks due to an inhibition of sperma¬ togonial development followed by depletion of the seminiferous epithelium by maturation (Jackson, Fox & Craig, 1961). There is, however, no effect on androgenic function of the testes (Jackson et al, 1961) but the total gonado¬ trophin content of the pituitary is reduced (Kar, Jehan, Kamboj, Chowdhury & Chowdhury, 1967).…”