Hormonal antagonism to the antispermatogenic effect of ethylene-dimethanesulphonate in rats.

Abstract

For the most part, the antifertility actions of non-steroidal chemicals in male rats do not appear directly to involve the endocrine system (Jackson, 1970). In this species, administration of ethylenedimethanesulphonate (EDS) is accompanied by a temporary involution of both the ventral prostate and the seminal vesicles (Cooper & Jackson, 1970). This observation naturally led to an investigation of how far the antispermatogenic and antifertility actions of this compound involved the endocrine system, particularly the production and secretion of androgen. Treatment with EDS also inhibits the spermatogenic process in the mouse (Cooper & Jackson, 1970), in Japanese quail (Jones, Kominkova & Jackson, 1972) and in the parasitic worm, Schistosoma mansoni (Davies & Jackson, 1970). After a single dose of the compound (75 mg/kg intraperitoneally), rats were sterile by Week 2 and remained thus for about 8 weeks (Table 1) ; in the great majority, normal fertility was finally restored. The corresponding weekly fertility pattern from male rats given this dose of EDS whilst under a regimen of nine daily injections of testosterone propionate (TP) (3 mg daily subcutaneously, commencing 3 days before the dose of EDS and continuing for 5 days afterwards) indicated some protective action, but only upon post-meiotic cells (Table 1 ). This is probably related to the androgen dependence in the rat of meiotic and post-meiotic stages of spermatogenesis. Androgen is able to maintain the entire spermatogenic process in hypophysectomized rats (Boccabella, 1963; Neumann & von Berswordt-Wallrabe, 1966; Clermont & Harvey, 1967) so that in our experiments, the failure of testosterone to support the pre-meiotic stages against damage by EDS was unexpected. Treatment with TP alone at this dose level is known to produce a 20 to 30% inhibition of the