Studies on germinal effects of quercetin, a naturally occurring flavonoid

Abstract

Quercetin (3,3',4',5,7-pentahydroxyflavone) is one of the most widely occuring flavonoids ingested by man in food. It has been showen to be mutagenic in prokaryotes as well as in in vitro mammalian cell lines. In view of the unavoidability of ingesting them via a normal diet, there is a need to assess the potential genetic risk to man, due to flavonoid ingestion, using whole animal assays. Dominant lethal studies have been carried out in adult Swiss male mice and Wistar male rats to investigate the germinal effects of quercetin. Adult Swiss males were treated with 200, 300 or 400 mg/kg of quercetin dissolved in 60% dimethyl sulfoxide, intraperitoneally. In the rat study, 200 and 300 mg/kg of quercetin were used. Individually caged males were paired with untreated females for a week and six sequential matings were carried out. Two independent experiments in mice and a single experiment in rats constituted the study. Females were evaluated for inducted dominant lethality during the midterm of pregnancy. At 200 mg/kg dose of quercetin, there were no significant differences between control and the test group in pregnancy, total or live implantations in mice or rats during the whole test period that could be attributed to the flavonoid exposure. In mice at 300 and 400 mg/kg of quercetin, there was a profound reduction in fertility of the males during all six matings. The number of total and live implantations also decreased, particularly at the 400 mg/kg dose, although the sample size was too small to be statistically significant. Contrary to this, the rat study did not show any impairment of fertility, nor was there any substantial suppression of total and live implantations at the highest (300 mg/kg) dose tested. There were no significant differences between control and treated groups with regard to the number of dead implantations at any dosage level at any stage of the study in mice and rats. Thus, no post-implantation losses - a reliable measure of dominant lethal mutations - were induced by quercetin in mice or rats. The loss of fertility could be due to germinal cytotoxicity, oligospermia or impairment of fertilizing ability of the treated animals. Similarly, several non-genetic factors which can contribute to reduction of live implantations would have to be excluded before considering induction of preimplantation lethality due to quercetin ingestion. In view of the small sample size and the 7-day mating schedule used in the present study, dominant lethal effects of quercetin require investigation using a 4-day mating schedule.