The exposure of men to the nematocide
dibromochloropropane (
DBCP) has caused prolonged oligo- and
azoospermia, which occasionally reverses spontaneously. We recently demonstrated that in testes of rats treated with a dose of
DBCP sufficient to reduce the percentage of tubules producing differentiating germ cells (tubule differentiation index, TDI) to 20%, the tubules lacking differentiating cells contained type A spermatogonia. To determine whether these type A spermatogonia could be stimulated to differentiate, as had been demonstrated previously in other models of toxicant-induced
sterility, we suppressed intratesticular
testosterone and serum
follicle stimulating hormone (FSH) levels with the
GnRH agonist
Lupron (
leuprolide). When the
GnRH agonist was given for 10 weeks starting immediately after
DBCP exposure, the TDI was maintained at 94%. Even when
GnRH-agonist treatment was stopped at week 10, the TDI remained between 65 and 80% 10 weeks later. Late spermatid counts averaged 10 x 10(6) per testis for the
GnRH-agonist-treated rats at week 20 compared with 1.7 x 10(6) per testis in rats treated with only
DBCP. To determine whether spermatogonial differentiation could be stimulated after the TDI had declined to below 30%, we initiated
GnRH-agonist treatment 6 weeks after
DBCP exposure. The
GnRH treatment increased the TDI to 53% at week 16. These results indicate that, if the same principles apply to humans, suppression of
testosterone may be applied to restore spermatogenesis in men rendered azoospermic by
DBCP or other reproductive toxicants.