Studies on the testicular effects of vitamin A palmitate in the Sprague-Dawley rat.
The purpose of the research was to investigate the mechanism of reported vitamin A-induced testicular degeneration. Three studies of vitamin A toxicity were conducted in male Sprague-Dawley rats; a 10-day study with daily ip injections of retinol palmitate at doses of 0, 115,000 and 230,000 IU/kg/day in adult rats; a 10-day study with juvenile rats treated with 115,000 IU/kg/day, pair-fed controls and ad lib.-fed controls; a 13-wk dietary study in which retinol palmitate beadlets were mixed in the food of juvenile rats at doses of 0, 60,000, 120,000 and 200,000 IU/kg/day; a second untreated group was pair-fed to the high-dose group. Even at doses that produced overt signs of hypervitaminosis A and mortality, minimal or no changes were observed in the testes. In the 10-day ip studies, only a 20% incidence of treated juvenile rats (115,000 IU/kg) and adult rats (230,000 IU/kg) showed sloughing germ cells in some of the tubule lumens of the testes, but the structure and integrity of the seminiferous epithelium was completely intact. No change in testicular morphology or spermatid counts was observed in the 13-wk dietary study. In all studies, testicular weights of treated rats were not significantly reduced when corrected for body weight or compared with pair-fed controls. In the 10-day ip studies, serum testosterone levels of treated rats did not differ from the respective pair-fed control rats, but in the 13-wk study, a dose-related reduction in testosterone occurred that was considered to be a direct effect of chronic vitamin A treatment. Seminal vesicle weights were decreased, as would be expected with decreased testosterone levels. Adrenal weights were increased in all studies. These findings suggest that the testes of rat are resistant to orally administered vitamin A palmitate and only slightly affected by ip administration.
Bosakowski
T
T
Department of Toxicology and Pathology, Roche Research Center, Nutley, NJ 07110.
Levin
A A
AA
Edgcomb
J H
JH
D000818:Animals; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D000084562:Retinyl Esters; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013739:Testosterone / Q000097:blood; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000633:toxicity
D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D013739:Testosterone