Zearalenone: The Enemy of the Cow Breeding Program

In Brief

• ZEN binds to estrogen receptors and causes hormonal imbalances.
• ZEN is not detoxified by ruminal microbiota, instead its estrogenic effect is increased.
• The endocrine disruption caused by ZEN leads to reproduction failure.
• Reproductive efficiency in dairy farms represents massive economic losses.

Zearalenone's (ZEN) effects can impair reproduction and cause spontaneous abortions, resulting in enormous economic losses to dairy producers. Here's how to recognize--and treat--the effects of ZEN in dairy cattle.

When addressing mycotoxins on dairy farms it is common to focus on the direct losses in production and health status. With Zearalenone (ZEN), the worries are different: Since it has a very similar structure to estrogen, ZEN can bind to the receptors located in distinct areas of the body, such as the uterus, mammary gland, hypothalamus and pituitary gland and cause delays in reproduction, spontaneous abortions and other reproductive challenges.

Before discussing the impact of ZEN, it’s important to understand how estrogen works in a cow’s body. During the estrous cycle of a cow, estrogen concentration remains stable and low until the heat, or estrus, where it increases abruptly. Estrogen prepares the reproductive organs of the cow for breeding. It also influences behavior that encourages mating. A normal estrus lasts one day (plus or minus), and once it has passed, the concentration of estrogen reduces  again (Figure 1, adapted from Senger (2003).

Figure 1. Hormonal fluctuations along the estrus cycle

When ZEN is ingested and reaches the rumen, a sort of transformation of the molecule can occur. Compared to swine or poultry, ruminants are considered more resistant to mycotoxins since the microbiota that inhabits the rumen is supposed to act as a first line of defense against toxins. However, in the case of ZEN, this metabolization does not result in an actual detoxification. The two main resulting molecules of this metabolic process are α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL) which can be 60 or 0.2 times as estrogenic (respectively). Although most of the ZEN stays unaltered, the biggest portion of what gets degraded becomes α-ZEL (figure 1, Gruber-Dorninger, submitted manuscript) and the estrogenicity is increased. Thus, one can say that if the feed is contaminated, the passage through the rumen will make ZEN either remain as estrogenic or get worse, but not less harmful.

Figure 2. In vivo degradation of Zearalenone in rumen cannulated dairy cows (Gruber-Dorninger et al., submitted manuscript)

Dr. Christoforou did the pregnancy checks 30 days after insemination via embryonic test and an additional check with ultrasound. He found that an important number of cows had aborted and had cystic ovaries (>20 mm diameter). He indicated that finding ovarian cysts during winter in Cyprus is rare as it tends to be influenced by heat stress. He started suspecting ZEN contamination, so he followed the following steps:

1. Consulted a nutritionist: They discussed the symptoms with the farmer and determined that the onset of symptoms was close to the moment when a new batch of barley straw started to be fed. The nutritionist also suspected ZEN, so they sent the material to be analyzed.
2. Analyzed the feed: Samples were sent to be analyzed via Spectrum Top® 50, an LC-MS/MS method. They found that the barley straw was contaminated by 1380 ppb ZEN. This straw was fed at approx. 5 kg/head/day.

In this case the problem was more severe due to the concentration of ZEN in the feed, but in some cases the effects, although less dramatic, can still impact the reproduction of cows.

When ZEN binds to the estrogen receptors in  different tissues, endocrine disruption takes place. This is why typical behavior of heat can happen even if a cow is not in real estrus, for instance when pregnant. Some of the most important negative effects of ZEN are the following:

• Difficulty for heat detection: Most of the typical ways to detect heat are related to the cow’s behavior. Being exposed to ZEN can alter the cow’s behavior to make it appear she is in heat although she is not; this is known as a false heat. An imprecise heat detection leads to inefficacy of insemination and prolonged open days.
• Hormonal imbalances: Reproductive hormones are produced or not, responding to feedback from other hormones. When ZEN circulates in the blood and binds to the estrogen receptors in distinct areas, it alters the production and concentration of other hormones in the blood (Fushimi et al., 2014, 2015; Mahmoud et al., 2013). This effect is also called endocrine disruption.
• Ovarian cysts: Endocrine disruption can lead to ovarian cysts. Under ZEN exposure, more follicles are recruited than usual, however only one follicle can develop for ovulation. This accumulation of undeveloped follicles can lead to the production of ovarian cysts from relatively low contaminations e.g. 200 ppb of diet (Mahmoud et al., 2013). The main problem is the reproductive delay this may cause, plus the veterinary treatment required to re-establish a balance.
• Abortions: Due to ZEN exposition, alterations in the concentrations of progesterone can occur. Progesterone is also known as “the pregnancy hormone” because once an ovum has been successfully fertilized, it ensures that the physiological conditions in the cow are created to preserve the embryo. A possible alteration to this set of conditions can lead to spontaneous abortions, particularly in the first third of the pregnancy, as described by Kallela & Ettala (1984) and Weaver et al. (1986).
• Udder enlargement in heifers: As estrogen promotes the development of the udder, an early exposition to ZEN in young heifers can induce a premature development of the mammary gland. This is associated to future milking problems, mammary infections and can be a reason for removal from the herd (Bloomquist et al., 1982; Coppock et al., 1990).

Any sort of delay in the reproduction of dairy cows is a great economic concern. According to different authors (De Vries, 2006; Eicker & Fetrow, 2003; Hovingh, 2009), the cost of a cow spontaneously aborting can be 550-1200 USD, and every extra open day costs 5.20-6 USD (Cabrera, 2014). Additionally, breeding problems are one of the top reasons for cow replacement. A cow that takes longer to become pregnant has a 75% higher possibility of being culled (Cabrera, 2014).

• Considering the economics of cow reproduction, ZEN can negatively impact a dairy farm if not addressed properly. A deactivation strategy for this particular mycotoxin is necessary in order to ensure an adequate hormonal balance and successful reproduction.

References

Bloomquist, C., Davidson, J. N., & Pearson, E. G. (1982). Zearalenone toxicosis in prepubertal dairy heifers. Journal of the American Veterinary Medical Association.

Cabrera, V. E. (2014). Economics of fertility in high-yielding dairy cows on confined TMR systems. Animal, 8(s1), 211–221.

Coppock, R. W., Mostrom, M. S., Sparling, C. G., Jacobsen, B., & Ross, S. C. (1990). Apparent zearalenone intoxication in a dairy herd from feeding spoiled acid-treated corn. Veterinary and Human Toxicology, 32(3), 246–248.

De Vries, A. (2006). Economic value of pregnancy in dairy cattle. Journal of Dairy Science, 89(10), 3876–3885.

Eicker, S., & Fetrow, J. (2003). New tools for deciding when to replace used dairy cows. Proc. Kentucky Dairy Conf., Cave City, KY. Univ. Kentucky, Lexington, 33–46.

Fushimi, Y., Takagi, M., Hasunuma, H., Uno, S., Kokushi, E., Watanabe, U., Liu, J., Marey, M. A., Miyamoto, A., & Otoi, T. (2014). Application of mycotoxin adsorbent to cattle feed contaminated with zearalenone: Urinary zearalenone excretion and association with anti-Müllerian hormone. World Mycotoxin Journal, 7(3), 367–378.

Fushimi, Y., Takagi, M., Monniaux, D., Uno, S., Kokushi, E., Shinya, U., Kawashima, C., Otoi, T., Deguchi, E., & Fink‐Gremmels, J. (2015). Effects of Dietary Contamination by Zearalenone and Its Metabolites on Serum Anti‐Müllerian Hormone: Impact on the Reproductive Performance of Breeding Cows. Reproduction in Domestic Animals, 50(5), 834–839.

Hovingh, E. (2009). Abortions in dairy cattle I: Common causes of abortions.

Kallela, K., & Ettala, E. (1984). The oestrogenic Fusarium toxin (zearalenone) in hay as a cause of early abortions in the cow. Nordisk Veterinaermedicin, 36(9–10), 305–309.

Mahmoud, M. A., Ta, G., Leil, A. Z., & Mz, A. E. (2013). Effect of mycotoxin on reproductive performance in dairy cattle. Assiut Vet Med J, 59, 203–213.

Senger, P. L. (2003). Pathways to pregnancy and parturition. Current Conceptions. Inc. Pullman, WA, 144.

Weaver, G. A., Kurtz, H. J., Behrens, J. C., Robison, T. S., Seguin, B. E., Bates, F. Y., & Mirocha, C. J. (1986). Effect of zearalenone on the fertility of virgin dairy heifers. American Journal of Veterinary Research, 47(6), 1395.