The effect of experimental long-term exposure to low-dose zearalenone on uterine histology in sexually immature gilts.

The objective of this study was to determine whether long-term (48-day) oral administration of low-dose zearalenone (ZEA) resulted in changes in uterine histology in sexually immature gilts. The study involved 12 clinically healthy 2-month-old gilts with a determined immune status. The animals were randomly divided into two experimental groups (E1, n=4; E2, n=4) and a control group (C, n=4). ZEA (20 μg/kg bw for group E1 and 40 μg/kg bw for group E2) was administered in gelatin capsules per os before the morning feeding for 48 days; group C was given placebo rather than ZEA. The animals were then sacrificed and the uteri were subjected to histological examination. Low doses of ZEA (50% and 100% of no observable adverse effect levels values) induced experimental hyperestrogenism and stimulated the proliferation of nearly all uterine wall tissues, as shown by significant increases in the index of proliferation values. The accompanying uterine hyperaemia caused uterine reddening and swelling. Atypical endometrial hyperplasia (hyperplasia simplex atypica) could be interpreted as the endometrium's physiological response to an excessive level of endogenous and/or exogenous estrogenic stimuli. The results of this study and the effects of ZEA in the uterus suggest that there is a possibility of detrimental health effects when the level of endogenous estrogens is low and the body is supplied with an additional dose of exogenous estrogens. Such effects probably results from synergic interaction that produce hyperestrogenism and lead to excessive estrogenic stimulation.