Feeding ZEN-contaminated feed to gilts can have huge negative implications on animal health and performance. Konstantinos Sarantis explores the literature to explain why ZEN is so harmful to gilts and why a mycotoxin risk management program is essential.

Zearalenone (ZEN) is a mycotoxin produced by Fusarium graminearum, F. culmorum, F. crookwellense, F. equiseti and F. semitectum. This mycotoxin regularly co-exists with deoxynivalenol (DON), as the same fungi (F. graminearum or F. culmorum) can produce both compounds. ZEN contamination in grains varies. According to the 2021 DSM Mycotoxin Survey, ZEN is the third most prevalent mycotoxin in Asia and South America (download the full report here).

The guidance levels for ZEN in animal feed, introduced by the European Commission, are 0.25 mg/kg in complementary and complete feeding stuffs for sows and fattening pigs, and 0.1 mg/kg in the same commodities for piglets and gilts.

Once ZEN is ingested, part is transformed to its metabolites, α-zearalenol and β-zearalenol. In pigs, the main metabolite is α-zearalenol. The toxicity of this metabolite is four-fold higher, which explains the higher sensitivity of pigs to ZEN. The effects and intoxication of ZEN depends on the amount ingested, length of exposure, age and reproductive phase of the animal.

The main effect of ZEN is on reproduction, by blocking the normal synthesis of hormones. ZEN resembles the estradiol molecule and competes with it for estradiol receptors (estrogenic receptors). These receptors can be found in different organs such as the liver, kidneys, testis, prostate gland, hypothalamus gland, pituitary gland, ovaries and intestines. This estrogenic effect disrupts the endocrine system, disturbing the hypothalamic-pituitary-ovarian axis and supressing follicle-stimulating hormone (FSH) secretion in the ovaries.

Table 1: The main effects of ZEN in pigs. (Source DSM)

ZEN effect in gilts

Due to their undeveloped endocrine system, gilts are even more sensitive to the estrogenic effects of ZEN. The results of ZEN ingestion are; hyperaemia and vulva swelling (hyperestrogenism), uterus mass increase, ovarian follicle atresia and atrophic ovaries, and vaginal or rectal prolapse.

Hyperestrogenism has been documented in gilts at different ages (from post weaning to ovulation) and at various contaminated feed levels. In four-month-old gilts fed ZEN contaminated feed, mild hyperestrogenism occurred a few days after ingestion (Obremski et al., 2003). In another study (Oliver et al., 2012), weaned gilts fed ZEN had a 2.4 times heavier total reproductive tract and 50% greater endometrial gland mass. This hyperestrogenism would delay oestrus onset and compromise the fertility and subsequent reproductive life of the gilt.

In-house research conducted by BIOMIN gave the same observations in Mycofix® Plus product efficacy trials. Gilts that ingested ZEN had a higher vulva volume (Figure 1) and reproductive tract weight (Figure 2). In addition, histopathological examination showed tissue degeneration in the presence of ZEN.

In addition, ZEN could compromise corpora lutea, ovary size, fertility, and increase abortion rates in first parity (Zwierzchowski et al., 2005). In a recent paper, when ZEN was ingested by post weaning gilts, the luteinizing hormone decreased in a dose dependent manner. Other clinical signs were hyperplasia of submucosal muscles, a decrease in the size of the cortex follicle, and degeneration and structural abnormalities of the reproductive tract (Chen et al., 2015). Moreover, high doses of ZEN may lead to anoestrus, which is a result of early puberty with infertility (no ovulation) (Kanora & Maes, 2009). Tiemann and Danicke (2006) report similar results in a review. Fifty percent of gilts confirmed anoestrus. Corpora lutea were maintained, mimicking pregnancy. Thus, ovulation could not occur and gilts were in a pseudo-pregnant state with uterus weight 2-fold heavier.

ZEN, as a mycoestrogen molecule, has multi-specificity. This means that it has more than one biological target. Estrogen receptors are distributed among different tissues and organs. ZEN and its metabolites, a part of the negative effect on reproductive system, can influence gene expression and the immune system and gastrointestinal tract.

Gastrointestinal tract

ZEN and its metabolites are an endocrine disrupting chemical, interacting with tissues and cells involved in the hormonal system. ZEN is not bio-transformed in the gastrointestinal tract. It is bio-transformed into its metabolites mainly in the liver and then it passes into the blood circulation. It then accumulates in different parts of the digestive tract including the duodenum, jejunum and descending colon.

However, ZEN interacts with estrogen receptors that are present in the gastrointestinal system. These receptors control cell proliferation and differentiation. As a result, apoptotic mechanisms are induced, leading to cell death and microflora imbalances. In addition, ZEN interaction with estrogen receptors impairs gastric motility, decreases intestinal permeability and inhibits intestinal secretion. Lowering the pace of gastric emptying creates tension in the anus, which may explain rectal prolapses.

Immunity

ZEN may also affect innate and adaptive immunity. As well as reproductive organ inflammation, ZEN can induce inflammation in immune organs. In ZEN exposed gilts, inflammation in mucosa and epithelium cells occurs, impairing intestinal defence.

Daniela et al. (2010), conducted in vitro studies in which ZEN reduced neutrophil viability and triggered an oxidative response. Both parameters play a pivotal role on the innate immune defence system. In a later in vivo study by the same group (2013) in weanling piglets, the effect of ZEN on immunocompetent tissues was studied. In the liver, ZEN mainly impaired functionality resulting in a hepatotoxic effect, and secondly reduced inflammatory response resulting in an immunotoxic effect. In the blood, lymphocyte proliferation was reduced and the synthesis of inflammatory cytokines increased. In the spleen, induction of an inflammatory response did not allow an adequate response to oxidative stress that was induced by ZEN.

The full role of ZEN on the immune system has not been fully investigated, especially the role of ZEN on vaccination efficacy. However, in-house research has shown that ZEN and DON have a negative impact on immune parameters (chemotactic index, macrophage activity) when ingested in weaning piglets (Table 2).

In this text, the effect of ZEN has been reviewed focusing in pre-pubertal gilts. Reflecting the frequency in which more than one Fusarium toxin is detected in feeds, the synergies between Fusarium mycotoxins should not be neglected. Co-contaminations, regardless of whether they show additive or synergistic effects, could cause further negative effects in animals, especially in the highly sensitive pig species. Therefore, a proper mycotoxin risk management program is obligatory.

Table 1. Effect in immunity parameters for gilts intoxicated with combination of DON and ZEN

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Article made possible through the contribution of Konstantinos Sarantis and BIOMIN

Zearalenone - a known but underestimated risk in gilts