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

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.

Practical Application of Urinary Zearalenone Monitoring System for Feed Hygiene Management of a Japanese Black Cattle Breeding Herd—The Relationship between Monthly Anti-Müllerian Hormone and Serum Amyloid A Concentrations

“…Currently, many reports have aimed to clarify and prevent the harmful effects of mycotoxins at each stage focused on three major factors. First, the characters, toxicity, and metabolites against the organs and/or systemic function of each mycotoxin (including emerging mycotoxins such as enniatin, beauvericine, and emodin) with both in vitro and in vivo approaches [20,21]. Second, the detection methods for these mycotoxins (including the case of multiple mycotoxins coexistence with different spp.…”

Phytoestrogens and Health Effects

“…This apparent discrepancy may be linked to the dose of exposure. According to a recent review [ 222 ], there are no epidemiological data on the reproductive effects of zearalenone and its metabolites. However, many data are available in rodent models, showing that at doses from 0.2 mg up to 146 mg/day the mycotoxins can alter follicular profiles in the ovaries of non-pregnant females, disrupt oestrus cycling, and increase myometrium thickness.…”

Overview of Bioactive Fungal Secondary Metabolites: Cytotoxic and Antimicrobial Compounds

“…This estrogenic mycotoxin is obtained from the fermentation of zearalenone by a highly reducing and non-reducing PKS, followed by hydrogenation to form α-zearalanol (29) . The synthetic version of α-ZAL, zeranol, is marketed as a growth promotor in the United States and Canadian livestock industries, whereas experimental animal models have typically demonstrated impaired growth following prenatal exposure [ 118 ].…”