Imbalance in the Blood Concentrations of Selected Steroids in Pre-pubertal Gilts Depending on the Time of Exposure to Low Doses of Zearalenone

Abstract

Zearalenone (ZEN) is a mycotoxin that not only binds to estrogen receptors, but also interacts with steroidogenic enzymes and acts as an endocrine disruptor. The aim of this study was to verify the hypothesis that low doses, minimal anticipated biological effect level (MABEL), no-observed-adverse-effect level (NOAEL) and lowest-adverse-effect level (LOAEL), of ZEN administered orally for 42 days can induce changes in the peripheral blood concentrations of selected steroid hormones (estradiol, progesterone and testosterone) in pre-pubertal gilts. The experiment was performed on 60 clinically healthy gilts with average BW of 14.5 ± 2 kg, divided into three experimental groups and a control group. Group ZEN5 animals were orally administered ZEN at 5 μg ZEN/kg BW, group ZEN10 — at 10 μg ZEN/kg BW, group ZEN15 — at 15 μg ZEN/kg BW, whereas group C received a placebo. Five gilts from every group were euthanized on analytical dates 1, 2 and 3 (days 7, 14 and 42 of the experiment). Qualitative and quantitative changes in the biotransformation of low ZEN doses were observed. These processes were least pronounced in group ZEN5 (MABEL dose) where ZEN metabolites were not detected on the first analytical date, and where β-ZEL was the predominant metabolite on successive dates. The above was accompanied by an increase in the concentration of estradiol (E2) which, together with “free ZEN”, probably suppressed progesterone (P4) and testosterone (T) levels.

The Effect of Different Doses of Zearalenone in Feed on the Bioavailability of Zearalenone and Alpha-Zearalenol, and the Concentrations of Estradiol and Testosterone in the Peripheral Blood of Pre-Pubertal Gilts

“…The presence of E 2 (see Figure 3) was not observed on the first nine sampling dates (19 days) of the experiment. On successive sampling dates (15 dates, 53.33%), E 2 values were higher in both E groups than in group C. The concentrations of T (see Figure 4) were lower on 60% sampling dates in both experimental groups than in the control group, which provides indirect evidence for the acceleration of metabolic processes or the conversion of T to E 2 [39] under the suppressive influence of ZEN [34,[40][41][42]. The concentrations of E 2 after 20 days of exposure and serum T levels throughout the experiment were directly proportional to the ZEN dose.…”

“…This observation points to a counter response to the presence of specific ZEN doses in pre-pubertal gilts. The presented results can be extrapolated [19,33,34] to suggest that "free ZEN" is captured by estrogen receptors (ERs) in the digestive tract [36], and that it stimulates qualitative changes (activation?) of ERs.…”

“…The resulting "free ZEN" can be utilized for specific purposes [17], for example, for competing with endogenous E 2 or coregulating its supply. The above is illustrated by the fact that both doses lead to a significant increase in the concentrations that induce hyperestrogenism although rather supraphysiological hormone levels (increase in the concentrations of E 2 in both E groups and increase in T levels in group EII relative to group C) [34,35]. This observation points to a counter response to the presence of specific ZEN doses in pre-pubertal gilts.…”

“…These findings indicate that the bioavailability of ZEN was higher in group EII, but they do not prove that ZEN was more effectively utilized for physiological processes. Low values of ZON at the beginning of the experiment can probably be attributed to the "saturation" of digestive tract tissues, in particular in regions with a higher concentration of ERs [19,36], and the low concentrations of endogenous hormones in animals during sexual maturation [5,8,34,37]. In other words, the involvement of the analyzed hormones in the stimulation of steroidogenesis and the conversion of T to E 2 ultimately led to supraphysiological hormone levels, in particular in group EII.…”

“…It should also be noted that those values are inversely proportional to the ZEN dose (see Figure 5). Therefore, exposure to a lower ZEN dose leads to a hormetic dose response [32] by influencing the concentrations of the parent compound and its metabolite in peripheral blood, as well as the synthesis and secretion of sex steroid hormones (see Figures 3 and 4) [31,33,34]. The above state limits bioavailability.…”