Characterization of cis-platinum-induced Sertoli cell dysfunction in rodents.
The present study examined the effects of dosage and frequency of cis-platinum administration on various aspects of Sertoli cell function and its correlation with the status of spermatogenesis in rats 1 and 9 weeks after the initial drug administration. Adult male Sprague-Dawley rats were administered cis-platinum (10 mg/kg) intraperitoneally as a single dose or as five daily doses of 2 mg/kg. Electron microscopic observation of testicular tissues fixed in the presence of lanthanum revealed that cis-platinum administration resulted in leakage of the Sertoli cell tight junctions. This occurred as early as 24 hr after the five daily injections, and persisted at least 40 days. Testicular androgen-binding protein (ABP) content was not significantly affected by either treatment regimen after 1 or 9 weeks of recovery. On the other hand, serum ABP values were significantly elevated after 9 weeks of recovery. In addition, the increased sodium and decreased potassium concentrations in seminiferous tubular fluid noted in cis-platinum-treated animals were also indicative of abnormal Sertoli cell secretory function. Degeneration of spermatogenic cells was noted as early as 5 days after the last drug administration; and partial restoration of spermatogenesis was noted after 40 days of recovery. We conclude that in rats both morphological and biochemical properties of Sertoli cells are affected by cis-platinum administration. These changes in Sertoli cell function may be responsible for the cis-platinum-induced impairment of spermatogenesis in these animals.
Pogach
L M
LM
Department of Medicine, East Orange Veterans Administration Medical Center, New Jersey 07019.
Lee
Y
Y
Gould
S
S
Giglio
W
W
Meyenhofer
M
M
Huang
H F
HF
D000727:Androgen-Binding Protein / Q000032:analysis; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004573:Electrolytes / Q000032:analysis; D007365:Intercellular Junctions / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012708:Sertoli Cells / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D013091:Spermatogenesis / Q000187:drug effects; D013739:Testosterone / Q000032:analysis
D000727:Androgen-Binding Protein; D004573:Electrolytes; D013739:Testosterone; D002945:Cisplatin