Many of us are familiar with the term "Nemesis" from the "Transformers" movie franchise, where Nemesis Prime is the antagonist to Optimus Prime. However, in this article, we will not discuss Optimus Prime. Instead, we will focus on zearalenone, a mycotoxin that poses a significant threat to fertility, effectively acting as its Nemesis.
Mycotoxins are toxic secondary metabolites produced by fungi species such as Aspergillus, Penicillium, and Fusarium, which infect agricultural commodities both in the field and during storage. These mycotoxins are known to cause severe health issues in humans, including liver cancer, Balkan endemic nephropathy, child growth impairment, immune suppression, neural tube defects, and even death from acute exposure. Emerging evidence also indicates that mycotoxins can negatively impact human fertility. Studies in animals and cell models have shown that mycotoxins like zearalenone, deoxynivalenol, ochratoxin A, and aflatoxin B1 can harm sex organs, gametes, and disrupt steroidogenesis, thereby affecting fertility(Eze et al., 2018).
Mycotoxin contamination is particularly problematic in developing countries due to favorable conditions for fungal growth and a lack of regulations to monitor and control contamination. Consequently, these regions often report higher levels of multiple mycotoxins in food and feed, posing significant health risks(Balló et al., 2023).
Infertility is on the rise in both developed and developing countries. Epidemiological studies indicate that 12% of assisted reproductive treatments (ART) occur in Scandinavian countries, Switzerland, the Netherlands, and the United Kingdom. Over the past 20 years, data reveal that in about 30% of infertility cases, the pathology is found solely in men, and in another 20%, both partners have abnormal pathologies. Therefore, male factors contribute to approximately 50% of infertility cases(Balló et al., 2023; Eze et al., 2018).
Zearalenone (ZEA) is a non-steroidal estrogenic mycotoxin produced by several fungi of the Fusarium sp. that contaminates cereal crops such as maize, barley, wheat, oats, sorghum, and sesame grains across the world. ZEA is genotoxic, immunotoxic, and tumorigenic, and it affects reproductive and developmental processes. It decreases fertility, reduces litter size, alters the weight of adrenal, thyroid, and pituitary glands in offspring, and changes the progesterone and estradiol levels. Recent studies have shown that reproductive disorders in humans and farm animals with hyperestrogenic syndrome are attributed to ZEA(Zheng et al., 2016).
Steroid hormones are essential for the proper development and function of reproductive organs in both humans and animals. In females, estrogen and progesterone support ovarian functions, including follicular development, oocyte maturation, and the regulation of ovulation. In males, testosterone (T) and 5α-dihydrotestosterone (DHT) are key hormones regulating spermatogenesis. Additionally, estrogen plays a role in spermatogenesis by stimulating germ cell proliferation, differentiation, maturation of spermatids, and germ cell survival and apoptosis. Steroidogenesis, the production of steroid hormones, involves the conversion of cholesterol to progestagens, which are then metabolized into androgens and estrogens, such as estrone and 17β-estradiol.
Recent reports show that Zearalenone and its metabolites (α-zearalenol (α-ZOL), β-zearalenol (β-ZOL), are known to bind oestrogen receptors (ER-α - and β) disrupting the binding of 17- β-oestradiol and also interfere with genes encoding for cytochrome P450 (CYP) and hydroxysteroid dehydrogenase (HSD) enzymes involved in steroidogenesis(Eze et al., 2018; Zheng et al., 2016).
Zearalenone (ZEA) represents a significant threat to fertility, acting as a "nemesis" to reproductive health. This mycotoxin, produced by Fusarium species, contaminates various cereal crops and exerts estrogenic effects that disrupt normal reproductive processes in both humans and animals. The adverse effects of ZEA include reduced fertility, altered hormone levels, and reproductive organ damage, highlighting the urgent need for effective mitigation strategies
References
Balló, A., Busznyákné Székvári, K., Czétány, P., Márk, L., Török, A., Szántó, Á., Máté, G., 2023. Estrogenic and Non-Estrogenic Disruptor Effect of Zearalenone on Male Reproduction: A Review. Int. J. Mol. Sci. https://doi.org/10.3390/ijms24021578
Eze, U.A., Lewis, S.E.M., Connolly, L., Gong, Y.Y., 2018. Mycotoxins as potential cause of human infertility – a review of evidence from animal and cellular models. Acta Hortic. 1225, 513–525. https://doi.org/10.17660/ActaHortic.2018.1225.70
Zheng, W.L., Pan, S.Y., Wang, G., Wang, Y.J., Liu, Q., Gu, J.H., Yuan, Y., Liu, X.Z., Liu, Z.P., Bian, J.C., 2016. Zearalenone impairs the male reproductive system functions via inducing structural and functional alterations of sertoli cells. Environ. Toxicol. Pharmacol. 42, 146–155. https://doi.org/10.1016/j.etap.2016.01.013
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