New and traditional approaches for the assessment of testicular toxicity.
In this study, the suitability of several methods for the assessment of testicular damage, including histopathology, flow cytometry (FCM), testicular sperm head counts, and secretion of androgen binding protein (ABP), has been evaluated. Testicular toxicity after acute exposure of adult rats to different doses of the known toxicant 1,3-dinitrobenzene (DNB) was analyzed. The effects showed dose dependence, in spite of the large variability within each dose group. Histopathology and FCM showed germ cell depletion, particularly of round spermatids; testicular sperm head counts were reduced and ABP production was increased. All evaluated methods showed similar sensitivities. The increased testicular ABP levels support the theory that the Sertoli cell is the likely target of DNB induced testicular toxicity, producing subsequent germ cell depletion. The presented results show the suitability of FCM for the analysis of testicular damage and also support the usefulness of including a metabolic marker for Sertoli cell function.
Suter
L
L
Pharma Non Clinical R&D, Toxicology, F. Hoffman-La Roche Ltd., Basle, Switzerland.
Clemann
N
N
Koch
E
E
Bobadilla
M
M
Bechter
R
R
D000727:Androgen-Binding Protein / Q000032:analysis; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004136:Dinitrobenzenes / Q000633:toxicity; D005434:Flow Cytometry; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000187:drug effects; D013076:Sperm Count / Q000187:drug effects; D013077:Sperm Head / Q000187:drug effects; D013733:Testicular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects; D014116:Toxicology / Q000379:methods*
D000727:Androgen-Binding Protein; D004136:Dinitrobenzenes; C017906:3-dinitrobenzene