Abstract
Contamination of the world’s food supply and animal feed with mycotoxins is a growing concern as global temperatures rise and promote the growth of fungus. Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium fungi, is a common contaminant of cereal grains and has also been detected at lower levels in meat, milk, and spices. ZEN’s synthetic derivative, zeranol, is used as a growth promoter in United States (US) and Canadian beef production. Experimental research suggests that ZEN and zeranol disrupt the endocrine and reproductive systems, leading to infertility, polycystic ovarian syndrome-like phenotypes, pregnancy loss, and low birth weight. With widespread human dietary exposure and growing experimental evidence of endocrine-disrupting properties, a comprehensive review of the impact of ZEN, zeranol, and their metabolites on the female reproductive system is warranted. The objective of this systematic review was to summarize the in vitro, in vivo, and epidemiological literature and evaluate the potential impact of ZEN, zeranol, and their metabolites (commonly referred to as mycoestrogens) on female reproductive outcomes. We conducted a systematic review (PROSPERO registration CRD42020166469) of the literature (2000–2020) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The data sources were primary literature published in English obtained from searching PubMed, Web of Science, and Scopus. The ToxR tool was applied to assess risk of bias. In vitro and in vivo studies (n = 104) were identified and, overall, evidence consistently supported adverse effects of mycoestrogens on physiological processes, organs, and tissues associated with female reproduction. In non-pregnant animals, mycoestrogens alter follicular profiles in the ovary, disrupt estrus cycling, and increase myometrium thickness. Furthermore, during pregnancy, mycoestrogen exposure contributes to placental hemorrhage, stillbirth, and impaired fetal growth. No epidemiological studies fitting the inclusion criteria were identified.
Highlights
Zearalenone (ZEN) is a secondary metabolite of Fusarium fungi and is one of the most common mycotoxin contaminants in global food supplies [1]
Title screening in Endnote eliminated 1278 articles that did not meet inclusion criteria outlined in the review protocol and PECO statement (Table 1). 2041 articles were assessed by title and abstract in Rayyan QCRI, and 1893 were excluded because they did not meet inclusion criteria, full text articles could not be accessed (n = 6) or were published prior to 2000
148 papers were read for full text eligibility and reviewed for risk of bias (RoB) using ToxR, of which 104 studies were included in the narrative review based on Klimisch scores of 1 or 2 (ToxR scores for all reviewed full texts are provided in Supplementary Table S2)
Summary
Zearalenone (ZEN) is a secondary metabolite of Fusarium fungi and is one of the most common mycotoxin contaminants in global food supplies [1]. ZEN contaminates cereal grains (e.g., maize, wheat, barley, oats and sorghum), and is widely detected in processed foods (i.e., pasta, breakfast cereal and bread) [1,2,3]. Several studies have documented ZEN concentrations in foodstuffs above established European Union (EU) maximum contamination limits (100–200 μg/kg for unprocessed cereals, 75 μg/kg for processed cereals) as summarized in a recent review [2]. Given mounting evidence of widespread mycoestrogen contamination in the food supply as well changes in climate promoting their growth, there is a clear need for additional investigation [6,7,8]
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