The effect of low-dose experimental zearalenone intoxication on the immunoexpression of estrogen receptors in the ovaries of pre-pubertal bitches

Abstract

Zearalenone is an estrogenic mycotoxin that often contaminates plant material used in the production of feeds for companion animals. Small daily doses of ingested zearalenone -a competitive substrate modulating the activity of enzymes participating in estrogen biosynthesis at the pre-receptor level -can induce subclinical symptoms of hyperestrogenism in bitches. The objective of this study was to determine the effects of low zearalenone doses on the presence of estrogen receptors in the ovaries of pre-pubertal Beagle bitches. The bitches were divided into three groups of 10 animals each: experimental group I -50 μg zearalenone/kg body weight administered once daily per os; experimental group II -75 μg zearalenone/kg body weight administered once daily per os; control group -placebo containing no ZEN administered per os. The animals were ovariorectomized at the end of the experiment, at 112 days of age. Estrogen receptors were detected in ovarian specimens by immunohistochemical methods. The results revealed an absence of estrogen receptors alpha in all groups. In both experimental groups a decrease in the positive response of estrogen receptors beta in specified structures of ovaries was observed. Very low α-zearalenol levels probably attested to the slowing down (hypostimulation) of the biotransformation process. Overall, zearalenone intoxication led to hyperestrogenism during a specific developmental stage of pre-pubertal bitches. As regards hormesis, the threshold dose of zearalenone (adaptive capability) was exceeded in the ovaries of experimental group II animals. The results obtained in both experimental groups suggest that long-term exposure to low-dose zearalenone intoxication decreased the degree of estrogen receptors beta staining in particular structures of ovaries in the experimental bitches, which initiated epigenetic modification mechanisms that inhibited ovarian development.

The effect of experimental low zearalenone intoxication on ovarian follicles in pre-pubertal bitches

“…In view of the characteristic properties of oestrogen, it could be inferred that the administration of ZEN induced the presence of large calcium deposits in the mitochondria, cellular debris, and residual oocytes in group EII. In another work (Gajęcka 2012) we have found the absence of a positive response to the presence of estrogen receptors ERα and results obtained in both experimental groups suggested that long-term exposure to low-dose ZEN intoxication decreased the positive response of ERβ receptors in the ovaries of experimental bitches, which initiated epigenetic modification mechanisms that inhibited (rather than regressed) the ovarian development.…”

The effects of experimental administration of low doses of zearalenone on the histology of ovaries in pre-pubertal bitches

“…ZEN affinity for ERβ of varies concentrations and the phase of the estrous cycle (Hatoya et al 2009). Locations of ER subtypes in the ovaries of various animal species reported by Korach et al (2003) and in our previous study (Gajęcka 2012) indicate that the changes observed in ovarian tissues could be induced by ZEN and α-ZOL effects on ERβ in the ovaries. It should also be noted that an increase in ZEN concentrations in feed is accompanied by a decrease in ERβ in ovarian tissues (Gajęcka 2012).…”

“…Locations of ER subtypes in the ovaries of various animal species reported by Korach et al (2003) and in our previous study (Gajęcka 2012) indicate that the changes observed in ovarian tissues could be induced by ZEN and α-ZOL effects on ERβ in the ovaries. It should also be noted that an increase in ZEN concentrations in feed is accompanied by a decrease in ERβ in ovarian tissues (Gajęcka 2012). The above could imply that congestion in the ovarian cortex is caused by non-genomic effects of estrogens (Bishop and Stormshak 2008).…”

“…Based on our knowledge of the correlations between endogenous steroids and estrogen receptors in animals, the effect of ZEN and its metabolites on ovarian function can be evaluated without analyzing estrogen receptors (Gajęcka 2012). This approach would explain the histological changes in the ovaries of pre-pubertal bitches.…”

“…cells containing ER proteins. In our previous study, the presence of only ERβ was found in pre-pubertal bitches (Gajęcka 2012). ZEN has higher affinity for ERα than to ERβ, and is a powerful antagonist of ERβ (Mueller et al 2004).…”