title: High risk of embryo-fetal toxicity: placental transfer of T-2 toxin and its major metabolite HT-2 toxin in BeWo cells.
abstract: Though T-2 toxin is the most harmful mycotoxin to the fetuses, it remains unclear whether T-2 toxin and its major metabolite, HT-2 toxin, could pass the placenta into the fetus and which kind of placental transport is involved in the passage. To illustrate their placenta transfer mechanism, the uptake and efflux of T-2 and HT-2 toxins across apical membranes of placenta with BeWo cells as a model were studied at different temperatures, pHs, and in the presence of transporter inhibitors with a developed liquid chromatography-tandem mass spectrometry to determine the amount of toxins in both fetal and maternal sites. Higher unidirectional transport of T-2 toxin was observed in the apical-to-basolateral direction than basolateral-to-apical one, whereas HT-2 toxin exhibited similar transport rate from the 2 directions. The main ATP-binding cassette transporters had no effect on the efflux of 2 toxins. Initial uptake of T-2 toxin was sodium dependent and saturable, and the apical uptake was temperature dependent and enhanced under acidic condition. The apical uptake of T-2 toxin was inhibited by metabolic inhibitors and the organic anion and organic cation transporter inhibitors. These results suggested that an active transport mechanism was responsible for the uptake of T-2 toxin, whereas passive diffusion was the principal mechanism for HT-2 toxin transport in the placenta. Taken together, these data characterized the placental transfer of T-2 and HT-2 toxins. The present study offered new ways of reducing the risks of T-2 and HT-2 toxins to both mother and fetuses.
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU)/Key Laboratory for the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.forename: Guyue
authors.initials: G
authors.lastname: Cheng
authors.forename: Lingli
authors.initials: L
authors.lastname: Huang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Chen
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Tao
authors.forename: Yuanhu
authors.initials: Y
authors.lastname: Pan
authors.forename: Haihong
authors.initials: H
authors.lastname: Hao
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wu
authors.forename: Dan
authors.initials: D
authors.lastname: Wan
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Liu
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wang
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D001693:Biological Transport, Active; D001711:Biotransformation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002853:Chromatography, Liquid; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D049990:Membrane Transport Modulators / Q000494:pharmacology; D008954:Models, Biological; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D018570:Risk Assessment; D012307:Risk Factors; D013605:T-2 Toxin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D053719:Tandem Mass Spectrometry; D013696:Temperature
chemical_list: D049990:Membrane Transport Modulators; D013605:T-2 Toxin; C012351:HT-2 toxin
keywords: BeWo cell model; HT-2 toxin; T-2 toxin; embryo-fetal toxicity; mycotoxin; placenta.