The inhibin B response to testicular toxicants ethylene glycol monomethyl ether or dibromoacetic acid in male rats.
BACKGROUND
This study was conducted as part of an ILSI-HESIconsortium effort to assess the utility of circulating inhibin B as an early biomarker of testicular toxicity in rats.


METHODS
Two known testicular toxicants were selected for use in this study: ethylene glycol monomethyl ether (EGME) and dibromoacetic acid (DBAA). EGME (200 mg/kg/day), DBAA (250 mg/kg/day), or vehicle control (0.2% hydroxypropyl methylcellulose [HPMC]) was administered orally to male rats for 3, 6, or 14 consecutive days. On study days 4, 7, and 15, serum was collected for evaluation of inhibin B levels from all surviving animals and a subset of animals was necropsied from each of the control, EGME, and DBAAgroups.


RESULTS
Administration of EGMEresulted in spermatocyte degeneration in late stage tubules and spermatocyte depletion to stage III on day 4, progressing to loss of spermatocytes and round spermatids to stage VI by day 7 and continued germ cell loss and degeneration of elongating spermatids by day 15. Inhibin B levels among EGME-treated animals progressively decreased relative to their respective controls at all time points. Administration of DBAA was associated with spermatid retention at all three time points and abnormal residual bodies at days 7 and 15. Inhibin B levels among DBAA-treated animals decreased progressively relative to their respective controls on days 7 and 15.


CONCLUSIONS
Serum inhibin B levels in rats provided a signal of testicular toxicity for each of these known testicular toxicants administered at high levels; however, histopathology provided the earliest evidence of toxic effects.
Department of Reproductive Toxicology, Preclinical Safety, AbbVie, North Chicago, IL 60064, USA.
Brian P
BP
Enright
Belen
B
Tornesi
Helga
H
Lorenz
Katharine
K
Whitney
D000085:Acetates / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005026:Ethylene Glycols / Q000008:administration & dosage / Q000633:toxicity*; D007265:Inhibins / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects* / Q000473:pathology*
D000085:Acetates; D005026:Ethylene Glycols; C422364:inhibin B; D007265:Inhibins; C088674:dibromoacetic acid; C005219:methyl cellosolve