Abstract
Ochratoxin A (OTA) is a mycotoxin produced by different Aspergillus and Penicillium species, and it is considered a common contaminant in food and animal feed worldwide. On the other hand, human embryonic stem cells (hESCs) have been suggested as a valuable model for evaluating drug embryotoxicity. In this study, we have evaluated potentially toxic effects of OTA in hESCs. By using in vitro culture techniques, specific cellular markers, and molecular biology procedures, we found that OTA produces mild cytotoxic effects in hESCs by inhibiting cell attachment, survival, and proliferation in a dose-dependent manner. Thus, we suggest that hESCs provide a valuable human and cellular model for toxicological studies regarding preimplantation stage of human fetal development.
Highlights
Evident toxic effects of Ochratoxin A (OTA) were observed after 8 h when approximately 60% of cells survived at a concentration of 10 ppm
OTA exposure studies have been developed on different cell lines of human and animal models, especially describing the mechanisms associated with increased levels of oxidative stress, DNA, and lipid and protein damage [38]
We evaluated the impact of OTA exposure in Human embryonic stem cells (ESCs) (hESCs) as a model for pre- and post-implantation of human embryos
Summary
Human pluripotent stem cells (hPSCs) represent heterogeneous populations, including induced pluripotent stem cells (iPSCs), endogenous plastic somatic cells, and embryonic stem cells (ESCs).Human ESCs (hESCs) are derived from the inner cell mass of the blastocyst, characterized by the ability to self-renew indefinitely and to give rise to all cell types of embryonic lineage (pluripotency) under the guidance of the appropriate chemical, mechanical, and environmental cues [1].There are high expectations regarding the use of hESCs for treating injuries and degenerative diseases, for modelling complex illnesses and developments, for screening and testing of pharmacological products, and for examining toxicity, mutagenicity, teratogenicity, and potential carcinogenic effects of a variety of environmental factors, including mycotoxins [2,3].Toxins 2019, 11, 217; doi:10.3390/toxins11040217 www.mdpi.com/journal/toxinsOchratoxin A (OTA) is the most abundant and toxic member of the ochratoxins, a group of secondary metabolites produced by fungi belonging to the genera Aspergillus and Penicillium [4,5,6,7].OTA can contaminate a wide variety of foods because of fungal infection in crops, in fields during growth, at harvest, or during storage and shipment. Human ESCs (hESCs) are derived from the inner cell mass of the blastocyst, characterized by the ability to self-renew indefinitely and to give rise to all cell types of embryonic lineage (pluripotency) under the guidance of the appropriate chemical, mechanical, and environmental cues [1]. There are high expectations regarding the use of hESCs for treating injuries and degenerative diseases, for modelling complex illnesses and developments, for screening and testing of pharmacological products, and for examining toxicity, mutagenicity, teratogenicity, and potential carcinogenic effects of a variety of environmental factors, including mycotoxins [2,3]. Besides cereals and cereal products, OTA is found in a range of other food commodities, including coffee, cocoa, wine, beer, pulses, spices, dried fruits, grape juice, pig kidney, and other meat and meat products from non-ruminant animals exposed to foodstuffs contaminated with this mycotoxin [8]
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