Dietary intake of high‐dose biotin inhibits spermatogenesis in young rats

Abstract

To characterize a new function of the watersoluble vitamin, biotin, in reproduction and early growth in mammals, the effects of high dietary doses of biotin on early spermatogenesis were biochemically and histologically investigated in male rats. Weaned rats were fed a CE-2 (control) diet containing 0.00004% biotin, or a control diet supplemented with 0.01%, 0.1%, or 1.0% biotin. Pair-fed rats were fed a control diet that was equal in calories to the amount ingested by the 1.0% biotin group, because food intake was decreased in the 1.0% biotin group. Food intake and body weight gain were lower in the 1.0% biotin group than in the control group. The kidney, brain and testis weights were significantly lower in the 1.0% biotin group than in the pair-fed group after 6 weeks of feeding. The accumulation of biotin in the liver and testis increased in a dose-dependent manner. In the 1.0% biotin group, the number of mature sperm was markedly lower, that of sperm with morphologically abnormal heads, mainly consisting of round heads, had increased. In addition, the development of seminiferous tubules was inhibited, and few spermatogonia and no spermatocytes were histologically observed. These results demonstrated that the long-term intake of high-dose biotin inhibited spermatogenesis in young male rats.

Dietary Biotin Supplementation Modifies Hepatic Morphology without Changes in Liver Toxicity Markers

“…These results agree with studies in normal rats showing that diets containing up to 1,000 mg/kg diet did not affect these parameters [21]. These data indicate that pharmacological concentrations of biotin do not affect classic liver damage tests.…”

“…We also found an increased number of binucleated hepatocytes (about 39%) and hepatocytes with nucleomegaly (66%) in the biotin-supplemented mice compared with the controls. These results together with previous results in pancreatic islets [15] and ovaries [19] and the observations by other groups [12, 21–23] indicate that pharmacological concentrations of biotin modify tissue structure.…”

“…Consistent with our experiments, they found that biotin did not affect normal body weight gain [20]; however, in contrast with our observations [19], they found estrus cycle irregularities. Sawamura et al [21], found that rats fed a diet containing 10 g biotin/kg diet for 6 weeks (990 mg/kg body weight) presented diminished total sperm counts and seminiferous tubule diameters compared to pair-fed rats. However, the biotin-supplemented group showed reduced food intake, impaired body weight gain, and decreased kidney and liver weights.…”

“…A lack of adverse effects has been reported in patients with inborn errors of biotin metabolism [46], normal individuals [24], diabetic patients [10, 13], and patients undergoing hemodialysis [11]. Rats fed diets containing up to 1,000 mg/kg diet did not show liver damage [21]. Although pharmacological concentrations of biotin are considered safe, further investigations are required to determine the effects of the tissue structure changes observed in this study.…”

“…Consistent with this effect of biotin on reproductive structures, acute biotin treatment induced atrophy in the corpora lutea of female rats [20]. In male rats, biotin supplementation for 6 weeks decreased total sperm counts as well as the diameter of the seminiferous tubes [21]. In animal models of diabetes, biotin supplementation ameliorated the histopathological morphology in the liver [12, 22], kidney [23], and pancreas [12].…”