Ethylene dimethanesulfonate inhibits the function of Sertoli cells in culture at sublethal doses

The dose-dependent effects of ethylene dimethanesulfonate (EDS) on transferrin production and viability of Sertoli cells in culture have been investigated. Sertoli cells, isolated from the testes of 20-day-old rats, exhibited decreased transferrin production in response to EDS at a dose of 0.3 mM. The suppression of transferrin synthesis by EDS reached a maximum (15% of control) with a dose of 1.1 mM, without significant cell mortality. An EDS dose of 2.7 mM proved lethal to Sertoli cells, reducing the number of viable cells per well by 85%. Sertoli cells preincubated with a sublethal dose of EDS (0.3-0.5 mM) appeared to recover upon removal of EDS from the culture medium, as evidenced by an increase in transferrin mRNA levels. Sertoli cells given 2.7 mM EDS did not recover. These data demonstrate a direct cytotoxic effect of EDS on Sertoli cell function at relatively low doses and a lethal effect of the alkylating agent at high doses. These results also indicate that EDS may affect Sertoli cells in vivo and, consequently, directly affect the function of the seminiferous epithelium.