Estrogenic and Non-Estrogenic Disruptor Effect of Zearalenone on Male Reproduction: A Review

Abstract

According to some estimates, at least 70% of feedstuffs and finished feeds are contaminated with one or more mycotoxins and, due to its significant prevalence, both animals and humans are highly likely to be exposed to these toxins. In addition to health risks, they also cause economic issues. From a healthcare point of view, zearalenone (ZEA) and its derivatives have been shown to exert many negative effects. Specifically, ZEA has hepatotoxicity, immunotoxicity, genotoxicity, carcinogenicity, intestinal toxicity, reproductive toxicity and endocrine disruption effects. Of these effects, male reproductive deterioration and processes that lead to this have been reviewed in this study. Papers are reviewed that demonstrate estrogenic effects of ZEA due to its analogy to estradiol and how these effects may influence male reproductive cells such as spermatozoa, Sertoli cells and Leydig cells. Data that employ epigenetic effects of ZEA are also discussed. We discuss literature data demonstrating that reactive oxygen species formation in ZEA-exposed cells plays a crucial role in diminished spermatogenesis; reduced sperm motility, viability and mitochondrial membrane potential; altered intracellular antioxidant enzyme activities; and increased rates of apoptosis and DNA fragmentation; thereby resulting in reduced pregnancy.

Toxicological Effects of Naturally Occurring Endocrine Disruptors on Various Human Health Targets: A Rapid Review

“…In particular, it has been reported that zearalenone shows a higher affinity with ERβ than ERα and acts in the pituitary gland through the non-classical estrogen membrane receptor G protein-coupled estrogen receptor 1 (GPR30) [ 53 ]. In addition, zearalenone is able to bind to albumin and sex hormone-binding globulin, thus enabling its release and entry into target cells via another estrogen pathway [ 12 ]. However, it is also important to note that zearalenone can have adverse effects on human health through both estrogenic and non-estrogenic pathways [ 12 ] and it is not possible to determine whether the observed effects are due to estrogenic or non-estrogenic activities.…”

“…In addition, zearalenone is able to bind to albumin and sex hormone-binding globulin, thus enabling its release and entry into target cells via another estrogen pathway [ 12 ]. However, it is also important to note that zearalenone can have adverse effects on human health through both estrogenic and non-estrogenic pathways [ 12 ] and it is not possible to determine whether the observed effects are due to estrogenic or non-estrogenic activities. Alternaria toxins such as alternariol and alternariol 9-methyl ether, derived from filamentous fungi of the Alternaria genus, exhibit endocrine-disrupting potential as estrogen receptor agonists [ 19 ] and may also activate other steroid receptors, such as the androgen and progesterone receptors.…”

“…In the mycotoxin class, the most extensively studied N-EDCs are alternariol and zearalenone, mycotoxins produced by the Alternaria genus [ 11 ] and Fusarium species, respectively, which can be ingested through food contamination and show endocrine-disrupting activity such as alterations of the male [ 12 ] and female reproductive system [ 13 ]. Several studies show that some cyanotoxins, secondary metabolites [ 14 ] produced by a variety of freshwater cyanobacteria, such as microcystins and cylindrospermopsin, can interfere with the endocrine system in mammals [ 15 ].…”

The biosynthetic logic and enzymatic machinery of approved fungi-derived pharmaceuticals and agricultural biopesticides

“…113 The hybrid PKS product 82 is analogous to the hormone 17-β-estradiol and capable of competitively binding to the receptors of estrogen influencing the hormone homeostasis. 114 α-Zearalenol (zeranol, Ralgro, α-ZOL, 83 ), a derivative of 82 , is widely used in the US and Canada as an anabolic agent in beef cattle and sheep for growth promotion. 115 As a non-steroidal estrogen, 83 is about four times as estrogenic as 82 , whereas the estrogenic effect of β-ZOL ( 84 ) is about equal to that of 82 .…”

“…Biosynthetically, aer the cyclization of 2,3(S)-oxidosqualene (111) into the tetracyclic precursor protosta-17(20)Z,24-dien-3bol (112) by FusA, two sequential oxidations on C-4 and C-16 occur by FusB4 and FusB2, producing 4b-carboxylic acid (113) and 16b-hydroxy-4b-carboxylic acid (114), respectively. Subsequent reactions include acetylation of the C-16 hydroxyl group, triggered by FusD, resulting in 16b-acetoxy-4b-carboxylic acid (115), and oxidation of the C-21 methyl group to carboxylic acid (116) by FusB3.…”