Gestational Exposure to Ethane Dimethanesulfonate: INTRODUCTION(1)


In 1964 Harold Jackson first described the antifertility effects of ethane dimethanesulfonate (EDS), an alkylating sulfonic ester first exploited for its potential in cancer chemotherapy. EDS has since been used as a prototypic agent to study the androgen dependency of spermatogenesis and Leydig cell (LC) ontogeny. EDS, unlike other compounds in its class that directly affect the spermatogenic epithelium, selectively and rapidly destroys LCs in the adult rat testis with a single injection of EDS (75 mg/kg). Serum testosterone (T) levels begin to decrease as early as 6 h after injection and are undetectable 9-10 days later.

Without androgen stimulation, spermatogenesis is suppressed and fertility is subsequently compromised; these alterations persist until LCs repopulate and resume androgen production. In the rat, the LC population is fully regenerated from undifferentiated progenitor cells by 49 days after injection and produces normal levels of T to restore and maintain spermatogenesis.

Further studies of the toxicology of EDS have revealed temporal, organ, and species differences with respect to effects on LCs. For example, EDS was found to be cytotoxic to LCs in neonatal and suckling rats. In neonatal rats dosed (Postnatal Day [PND] 5-16) s.c. with 50 mg/kg EDS, the fetal LC population is destroyed and the seminiferous tubules were permanently damaged either by direct cytotoxic effects prior to the formation of the blood-testis barrier or androgen deprivation resulting from fetal LC loss.