Fighting zearalenone: A different ball game

If one thinks of an oestrogen receptor as a baseball glove, its role is to catch oestrogen molecules and pass the signal on to the cells to react. <em>Photo: Janece Flippo, Shutterstock</em> — If one thinks of an oestrogen receptor as a baseball glove, its role is to catch oestrogen molecules and pass the signal on to the cells to react. *Photo: Janece Flippo, Shutterstock*

Due to its resemblance to oestrogen, some would rather call the mycotoxin zearalenone (ZEN) a myco-oestrogen than a mycotoxin. The compound being similar to oestrogen, however, reveals its effect: it can affect sows’ reproductive cycles.

Zearalenone (ZEN) commonly impacts pig reproduction and comes in many forms. The base molecule naturally goes through changes within fungi, plants and animals. Some of these changes are tiny, but have a big impact on potency – meaning that even low levels of ZEN can cause issues. The different forms can also explain why pigs are so sensitive to ZEN.

ZEN’s effects on vertebrate animals’ reproduction appears to be an accident of biology. ZEN plays no active role in fungal reproduction. Production of the mycotoxin seems to have developed simply so that some Fusarium fungi can inhibit the growth of other fungi and maintain a place on plant material. Toxicity to animals is relatively low, but ZEN bears a resemblance to oestrogen: that is why some prefer to call it a myco-oestrogen rather than a mycotoxin.

The baseball glove model

Oestrogen – a main reproductive hormone – plays a predominant role in sexual development and female fertility. A good balance of oestrogen levels is also important in male sexual development. The main form of oestrogen created inside animals is 17β-estradiol. This hormone interacts with the oestrogen receptors in the body regulating reproductive processes. The levels of estradiol fluctuate according to requirements in the reproductive cycle, but myco-oestrogens can upset this delicate balance.

If one thinks of an oestrogen receptor as a baseball glove, its role is to catch oestrogen molecules and pass the signal on to the cells to react. The receptors are pretty good at doing that, but they are not fool proof. ZEN fits into the baseball glove well enough that it triggers the same processes that oestrogen would, confusing the animal – with bad consequences for reproduction.

Unmasking hidden mycotoxins

Masked mycotoxins cannot be detected by some conventional analytical methods. During digestion, intestinal enzymes can cleave masked mycotoxins, releasing the parent mycotoxins and posing a risk to pigs. The most advanced, commercially available mycotoxin detection method (Spectrum 380) can identify over 380 different mycotoxins and metabolites, including many masked mycotoxins.

Depending on reproductive function and timing, ZEN’s potency has been considered three to ten times less than 17β-estradiol: in a recent assessment; perhaps around 470 times less (Table 1). In the liver and gut mucosa of animals, some zearalenone also have one hydrogen ion, forming alpha-zearalenol which has slightly more potency than 17β-estradiol itself and 560 times more oestrogenic than ZEN as it fits the baseball glove much better. At other times the oxygen and hydrogen point in a different direction. Beta-zearalenol, for example, is less oestrogenic than ZEN.

Why pigs are so sensitive

Pigs are far better than other animals at producing alpha-zearalenol than beta-zearalenol. This means they boost the oestrogenic activity rather than reduce it. Pig liver function is also poorer at combatting ZEN-type compounds. The livers of other animals are generally better at glucuronidation, and therefore detoxification, of some ZEN. So pigs are more sensitive than other animals. Gilts and piglets are among the most susceptible to ZEN’s effects. Foetuses and neonates have very little defense of their own, so mycotoxin carryover from the mother is a concern.

In combination with deoxynivalenol (DON), the mucosa reducing effects of DON are actually amplified. Small amounts of DON can increase ZEN’s effect on reproductive systems.

Within plants and even sometimes within fungi, ZEN may be hard to detect due to masking by sulfur compounds or sugars. While these masked forms are not oestrogenic (they don’t fit well in the baseball glove), they readily become oestrogenic again when the sulfur or sugar is removed in an animal’s digestive system. So, masked forms should be considered as potentially harmful to pigs and should be monitored in order to have a complete picture of the risk. The masked ZEN-14-sulfate form commonly accounts for around 20% of the total ZEN amount in feed material, but this figure can be much higher in some feeds.

Biotransformation beats binding

Binding only offers a partial solution to ZEN. Biomin had developed effective biotransformation strategies that structurally alter mycotoxins, making them non-toxic to animals, and have proven effective against many mycotoxins including ZEN-related compounds. This complements a binding strategy that works well against aflatoxins. Biotransformation takes place rapidly, cannot be reversed, and results in non-oestrogenic end products: ZEN compounds lose their shape and don’t fit into the baseball glove of an oestrogen receptor.

The complexities of ZEN

The complexity of the forms, timing with the animal’s processes and interactions with other mycotoxins make it hard to pin down just what the effect ZEN and its related compounds will have in a particular pig. So we need to be cautious about even seemingly low levels. Within the hormone system, there is a delicate balance to maintain. In addition to accurate testing of ZEN compounds, it therefore makes sense to maintain a risk management programme that includes biotransformation of ZEN compounds and effectively addresses other mycotoxins to safeguard the young and breeding pigs.