The research team’s study, just published in Scientific Reports, indicates that microRNAs (miRNAs) in porcine uterus and serum are affected by the feed contaminant zearalenone and therefore represent a promising new target for mycotoxin biomarker discovery.
The mycotoxin zearalenone (ZEN) poses a risk to animal health because of its xenoestrogenic effects. Over the past two decades, the potential health risks deriving from endocrine active substances in food and feed have become the focus of increasing public, scientific and regulatory attention. These substances comprise hundreds of environmental chemicals, such as bisphenol A, phthalates, atrazine, polychlorinated biphenyls, polybrominated diphenyl ethers or dichlorodiphenyltrichloroethane.
Typically, endocrine disruptors interfere with the endocrine system either by binding to hormone receptors (as agonist or antagonist), modulation of hormone receptor expression or affecting levels of circulating hormones.
ZEN is a frequent contaminant of cereal-based food and feed and acts as full and partial agonist on estrogen receptors α and β (ERα, Erβ). Diagnosis of ZEN-induced disorders remains challenging due to previous lack of appropriate biomarkers.
MiRNA ZEN biomarkers
However, the research team reports that circulating microRNAs (small non-coding RNAs) in porcine uterus and serum have remarkable biomarker potential, as they can serve as indicators for pathological processes in tissue.
The team combined untargeted and targeted transcriptomics approaches to investigate the effects of ZEN on the microRNA expression in porcine uterus, jejunum and serum, respectively.
The study involved 24 piglets in groups that received low (0.17 mg/kg), medium (1.46 mg/kg) and high (4.58 mg/kg) levels of ZEN in feed against a control group whose feed was uncontaminated.
After 28 days, the microRNA expression in the jejunum remained unaffected, while significant changes in the uterine microRNA profile were observed. Importantly, 14 microRNAs were commonly and dose-dependently affected in both the ZEN medium and ZEN high group, including microRNAs from the miR-503 cluster (i.e. ssc-miR-424-5p, ssc-miR-450a, ssc-miR-450b-5p, ssc-miR-450c-5p, ssc-miR-503 and ssc-miR-542-3p). Predicted target genes for those microRNAs are associated with regulation of gene expression and signal transduction (e.g. cell cycle).
Although the effects in serum were less pronounced, receiver operating characteristic analysis revealed that several microRNA ratios were able to discriminate properly between non-exposed and ZEN-exposed pigs (e.g. ssc-miR-135a-5p/ssc-miR-432-5p, ssc-miR-542-3p/ssc-miR-493-3p).
“This work sheds new light on the molecular mechanisms of ZEN, and fosters biomarker discovery,” commented TAmiRNA CEO and founder, Dr. Matthias Hackl, who led the TAmiRNA contingent on the team, who also included Dr. Susanna Skalicky. Lead author was Dr. Bertrand Grenier from Biomin Research Center (BRC) at Technopark, Tulln.
TAmiRNA specializes in technologies for profiling levels of blood-circulating microRNAs and developing multi-parametric classification algorithms (“signatures”). TAmiRNA uses these technologies to develop minimal-invasive diagnostic tests for drug development, early diagnosis and prognosis of disease, and as companion diagnostic tests to support treatment decisions.
More information available at: www.tamirna.com
Biomin is an animal health and nutrition company headquartered in Inzersdorf-Getzersdorf, Austria that develops and produces feed additives and premixes for livestock animals including swine, poultry, dairy and beef cattle as well as aquaculture.
The firm supplies customers in more than 100 countries throughout the world.
The Biomin Research Center (BRC) at Campus Tulln in Austria, employs 80 researchers engaged in applied basic research to lead the firm’s in-house R&D efforts, supported by a research network of 150 academic and research institutions worldwide.
More information about BRC at: https://www.biomin.net/about/research/
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