Time-Course Change of Testicular Toxicity with Thiamphenicol in Male Sprague-Dawley Rats

A total of 30 male Sprague-Dawley rats were treated orally with thiamphenicol (TAP) at 200 mg/kg/day for up to 4 weeks followed by 10 weeks recovery. At each week of treatment, 5 of them were examined weights of the testis and accessory genital glands, histology, staging analysis, and measurements of serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone (TES). At weeks 3 and 10 of recovery, 5 of them were quantified sperm counts and motility in addition to examinations of organ weights and histology. Cell proliferation activity was assessed at week 10 of recovery. Another group of 10 animals was provided as the vehicle control and examined the same parameters as mentioned above at week 4 of treatment or at week 10 of recovery. Weights of the seminal vesicles and prostate were significantly decreased during the treatment but showed a remarkable recovery after cessation of dosing. The testicular weights decreased rather mildly during the treatment but kept decreasing during the recovery period. In histology, damage of germ cells included apoptosis of germ cells, frequent occurrence of giant cells, and vacuolar spaces in the seminiferous tubules. In staging analysis, the first decreased indices were observed in spermatogonia (type B spermatogonia) in stage V and preleptotene spermatocytes in stage VII at week 2 of treatment. During recovery, an intact seminiferous tubule was seen neighboring to the other one showing “Sertoli only syndrome”. Cell proliferation activity was preserved in isolated cells on the basement membrane of “Sertoli only syndrome” seminiferous tubules. Considerable recovery was observed in sperm counts and motility. Serum TES and LH were decreased at week 4 of treatment but no effects on FSH. It is most likely that Sertoli cells are the primary target in TAP toxicity.