Testicular Toxicity of Thiamphenicol in Sprague-Dawley Rats

Groups of 12 male Sprague-Dawley rats received oral treatment with thiamphenicol (TAP) at a dose of 0, 100, or 200 mg/kg/day for 4 weeks and, then, 4 of each group were left untreated for further 13 weeks. After termination of treatment, they were mated with intact females to assess reproducitve potential, collected blood samples for measurement of serum hormones [luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone (TES)], necropsied, weighed the brain, pituitary, adrenals, testes, and accessory genital organs, and carried out histological examinations on the testis and epididymis including stage analysis of the seminiferous tubules. After the withdrawal period, histological observations on these organs were also conducted in all survivors. Retarded weight gain and decreases in weight of organs (organ /brain weight ratio) except adrenals were remarkably evident in rats at 200 mg/kg/day. Reproductive performance was successful in all treated groups except 2 males at 200 mg/kg/day which showed abnormal sperms in their morphology and distribution in the cauda epididymidis. Histological observations in rats at 200 mg/kg/day disclosed a variety of regressive changes of spermatocytes and spermatids including apoptosis, dissociation of cell arrangement, and frequent giant cell formation, suggesting that the primary target of TAP is those germ cells or Sertoli cells. Stage analysis of the seminiferous tubules of the testis showed decreased indices of all types of germ cells in rats at 100 mg/kg/day which manifested no particular changes in routine histological observations, indicating significance and high sensitivity of this analysis in assessment of testicular toxicity by chemicals. Serum levels of LH and TES were decreased in rats at 200 mg/kg/day but not changed at 100 mg/kg/day. After the withdrawal period, all testes from rats at 200 mg/kg/day showed so called “Sertoli only syndrome”. The present results may suggest that the role of Sertoli cells should be more highlighted in the consideration of mechanism of testicular toxicity of TAP.