Clinical effects and biochemical mechanisms associated with exposure to the mycoestrogen zearalenone

The mycoestrogen zearalenone (ZEA) is found worldwide as a contaminant in cereals and grains, including maize and soybeans. Despite its non-steroidal structure, ZEA activates estrogen receptors resulting in functional and morphological alteration in reproductive organs. Among farm animals, pigs are considered to be the most sensitive species, and clinical signs of exposure include ovarian atrophy, prolonged estrus intervals, persistent corpora lutea, decreased fertility and stillbirth. Controlled experiments demonstrated that the intensity of these effects depends upon the reproductive status and is more pronounced in prepubertal gilts. ZEA interacts not only with both types of estrogen receptors but is also a substrate for hydroxysteroid dehydrogenases, which convert it into two stereoisomeric metabolites, alpha-zearalenol and beta-zearalenol. A second reduction step yields the two minor metabolites alpha-zearalanol and beta-zearalanol. Alpha-hydroxylation results in an increase in estrogenic potency as compared to the parent compound, and the species-specific rate of alpha-hydroxylation may account for the susceptibility of certain animal species, including pigs, towards ZEA exposure. Another factor that might contribute to the species-specific sensitivity is the glucuronidation capacity inactivating ZEA as well as its metabolites. In comparison with other animal species, certain pig breeds have a low glucuronidation capacity, and hence this may cause a delayed inactivation of the ZEA. Experiments in vivo and in vitro indicate that ZEA and its metabolites are substrates for various enzymes involved in steroid metabolism. Hence, considering the interaction with estrogen receptors mentioned above and the modulation of enzyme kinetics, ZEA is grouped with the compounds known collectively as endocrine disrupters. This classification is substantiated by the findings that maternal exposure to ZEA affects the development and reproductive activity in the offspring (F1), as demonstrated in rodent studies. The diversity of biological effects also seems to account for the significant variability in the outcome of clinical trials conducted with pigs of different age groups, and suggests that adverse effects associated with exposure to ZEA occur at concentrations in feed that do not cause obvious clinical signs. (c) 2007 Elsevier B.V. All rights reserved.