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. 2021 May 24;13(6):373.
doi: 10.3390/toxins13060373.

Impact of Fusarium-Derived Mycoestrogens on Female Reproduction: A Systematic Review

Carolyn W Kinkade  1   2 , Zorimar Rivera-Núñez  2   3 , Ludwik Gorcyzca  4 , Lauren M Aleksunes  2   5   6 , Emily S Barrett  2   3
Affiliations

Impact of Fusarium-Derived Mycoestrogens on Female Reproduction: A Systematic Review

Carolyn W Kinkade et al. Toxins (Basel). .

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.

Keywords: female reproduction; fertility; mycoestrogen; mycotoxin; pregnancy; zearalenone; zeranol.

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Conflict of interest statement

The authors (Z.R.-N., L.G., L.M.A., and E.S.B.) receives grant support for research on this topic. The author (LA) has given talks on this topic at workshops, seminars, and conferences for which travel and accommodation has been paid for by the organizers. The other authors declare that they have no known conflicts of interest. Funding for this research is from: National Institute of Environmental Health Sciences [Grants F31ES029794, R01ES029275, T32ES019854, T32ES007148, and P30ES005022] and the National Center for Advancing Translational Sciences [Grant UL1TR003017].

Figures

Figure 1
Figure 1
Impact of mycoestrogens on female reproduction. Created with BioRender.com.
Figure 2
Figure 2
Phase 1 biotransformation of zearalenone (ZEN) by species. ZEN is metabolized by hydroxysteroid dehydrogenases (HSD) into biologically active metabolites, α-ZOL and β-zearalenol (β-ZOL) as well as zearalanone (ZAN). α-ZOL is further reduced to form zeranol (α-zearalanol).
Figure 3
Figure 3
PRISMA flow diagram.
See this image and copyright information in PMC

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