Effect of gender, pregnancy and exposure conditions on metabolism and distribution of zearalenone in rats

Abstract

The mycotoxin zearalenone (ZEA) is produced by a variety of Fusarium fungi and contaminates numerous cereals, fruits and vegetables. Interacting with the oestrogen receptors, ZEA and reduced metabolites zearalenols (ZOLs) cause hormonal effects in animals, such as abnormalities in the development of the reproductive tract and mammary gland in female offspring. Limited information is available on the pharmacokinetics of ZEA and its metabolites, particularly in pregnant females, foetuses and newborns. Our study was conducted to characterise the tissue distribution and metabolism of ZEA in male and female rats in various physiological states (virgin female, pregnant female) and exposure conditions (subcutaneous versus oral exposure, single versus repeated exposure to 1 mg/kg ZEA). Respective placental and mammary transfer to foetuses and newborns was evaluated. In all states and exposure conditions, α-ZOL and the glucuronides of ZEA and α-ZOL were the predominant metabolites, mostly concentrated in the intestine, the liver and the urine. Toxins were very low or undetectable in most of the tissues 24 h after ZEA exposure, except in foetal livers. Absorption and intestinal glucuronidation of ZEA were higher in males than females. α-ZOL concentration was significantly higher in the intestine and liver of males and pregnant females, compared to virgin females. ZEA and all its metabolites easily crossed the placental barrier and transferred into the milk. ZEA was metabolised in the foetal and neonatal stages, glucuronides being the main form detected in all organs. Metabolite elimination was slower in foetal tissues than in maternal tissues. All toxin concentrations in the foetal and neonatal tissues strongly increased in cases of repeated maternal exposure. A better knowledge of the metabolism and transfer of ZEA in foetuses and newborns will help to evaluate the health risk that such endocrine disruptors represent in these stages.