Dibromochloropropane inhibits spermatogonial development in rats.
Exposure to the nematocide dibromochloropropane (DBCP) has caused prolonged oligo- and azoospermia in men. There are questions regarding the cellular targets resulting in this effect. In this study we characterized an animal model, in which four daily injections of DBCP produced prolonged oligospermia in LBNF(1) rats without any indication of recovery. Between 6 and 20 weeks after DBCP treatment, 70% of seminiferous tubules showed an epithelium with Sertoli cells but no differentiating germ cells. About 20% of tubules contained differentiating germ cells and 10% showed occlusion or major morphologic alterations to Sertoli cells. Since gonadotropin levels and intratesticular testosterone (ITT) concentrations were elevated in the DBCP-treated rats, the failure of spermatogonial development could not have been a result of lack of these hormones. The tubules without differentiating germ cells contained actively proliferating and dividing type A spermatogonia, which underwent apoptosis instead of differentiation. Thus, the target for the damaging effect appears not to be the killing of stem spermatogonia, but the loss of their ability to undergo differentiation. The presence of type A spermatogonia in the atrophic tubules indicates the potential for intervention to restore spermatogenesis.
Meistrich
Marvin L
ML
M.D. Anderson Cancer Center, Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. meistrich@mdanderson.org
Wilson
Gene
G
Shuttlesworth
Gladis A
GA
Porter
Karen L
KL
D000818:Animals; D000969:Antinematodal Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006062:Gonadotropins / Q000097:blood; D007248:Infertility, Male / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D007267:Injections; D008297:Male; D011247:Pregnancy; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D012670:Seminiferous Epithelium / Q000187:drug effects / Q000473:pathology; D012671:Seminiferous Tubules / Q000187:drug effects* / Q000473:pathology; D012708:Sertoli Cells / Q000187:drug effects / Q000473:pathology; D013093:Spermatogonia / Q000187:drug effects* / Q000473:pathology; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D000969:Antinematodal Agents; D006062:Gonadotropins; D013739:Testosterone; C007318:1,2-dibromo-3-chloropropane; D011407:Propane