Restoration of spermatogenesis in dibromochloropropane (DBCP)-treated rats by hormone suppression.
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.
D000818:Animals; D000969:Antinematodal Agents / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000097:blood; D007279:Injections, Subcutaneous; D016729:Leuprolide / Q000627:therapeutic use*; D008297:Male; D009845:Oligospermia / Q000188:drug therapy*; D011407:Propane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013076:Sperm Count; D013087:Spermatids / Q000187:drug effects / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects* / Q000502:physiology; D013093:Spermatogonia / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D000969:Antinematodal Agents; D007987:Gonadotropin-Releasing Hormone; D005640:Follicle Stimulating Hormone; C007318:1,2-dibromo-3-chloropropane; D016729:Leuprolide; D011407:Propane