Inhibin B as a marker of sertoli cell damage and spermatogenic disturbance in the rat.
This study was designed to determine the effects of Compound A on spermatogenesis including assessment of inhibin B levels and on fertility in the male rat over a 15 to 19 weeks treatment and a 19 weeks treatment-free period in control and 30, 60, and 180 mg/kg dose groups (n = 22/group). Compound A in a dose-dependent manner induced various degrees of spermatogenic alterations compatible with Sertoli cells being the primary target, for example, inter- and intracellular Sertoli cell vacuolization and altered cellular morphology followed by germ cell degeneration and marked reduction of epididymidal sperm numbers. Blood-testis barrier remained intact (electron microscopy and hyperosmotic fixation test) until germ cells disappeared. Mating behavior and weights of androgen-dependent prostate and seminal vesicles remained unaffected. Inhibin B levels correlated only with moderate to severe spermatogenic alterations. Ten animals with inhibin B levels below detection limit were encountered and five of these animals were fertile in week 19 but following 19 weeks without treatment, another five animals were rendered infertile and inhibin B levels remained undetectable. In the rat, inhibin B only reflects major spermatogenic alterations and markedly reduced inhibin B levels might indicate irreversibility of these alterations and even infertility.
Preclinical Drug Safety, AiCuris GmbH & Co. KG, Wuppertal, Germany.
Tamara
T
Pfaff
Jon
J
Rhodes
Martin
M
Bergmann
Gerhard F
GF
Weinbauer
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D004822:Epididymis / Q000473:pathology; D005260:Female; D007265:Inhibins / Q000097:blood*; D008297:Male; D009929:Organ Size; D051381:Rats; D012098:Reproduction; D012670:Seminiferous Epithelium / Q000473:pathology; D012708:Sertoli Cells / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism
D015415:Biomarkers; C422364:inhibin B; D007265:Inhibins