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dc.contributor.authorLucendo-Villarin, B.
dc.contributor.authorFilis, P.
dc.contributor.authorSwortwood, M.J.
dc.date.accessioned2019-07-15T16:16:58Z
dc.date.available2019-07-15T16:16:58Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85019216839&doi=10.1007%2fs00204-017-1983-0&partnerID=40&md5=90562203083115b57e0a7c4ff20da2c9
dc.identifier.urihttp://hdl.handle.net/10713/10020
dc.description.abstractThe liver is a dynamic organ which is both multifunctional and highly regenerative. A major role of the liver is to process both endo and xenobiotics. Cigarettes are an example of a legal and widely used drug which can cause major health problems for adults and constitute a particular risk to the foetus, if the mother smokes during pregnancy. Cigarette smoke contains a complex mixture of thousands of different xenobiotics, including nicotine and polycyclic aromatic hydrocarbons. These affect foetal development in a sex-specific manner, inducing sex-dependant molecular responses in different organs. To date, the effect of maternal smoking on the foetal liver has been studied in vitro using cell lines, primary tissue and animal models. While these models have proven to be useful, poor cell phenotype, tissue scarcity, batch-to-batch variation and species differences have led to difficulties in data extrapolation toward human development. Therefore, in this study we have employed hepatoblasts, derived from pluripotent stem cells, to model the effects of xenobiotics from cigarette smoke on human hepatocyte development. Highly pure hepatocyte populations (>90%) were produced in vitro and exposed to factors present in cigarette smoke. Analysis of ATP levels revealed that, independent of the sex, the majority of smoking derivatives tested individually did not deplete ATP levels below 50%. However, following exposure to a cocktail of smoking derivatives, ATP production fell below 50% in a sex-dependent manner. This was paralleled by a loss metabolic activity and secretory ability in both female and male hepatocytes. Interestingly, cell depletion was less pronounced in female hepatocytes, whereas caspase activation was ~twofold greater, indicating sex differences in cell death upon exposure to the smoking derivatives tested. Copyright 2017, The Author(s).en_US
dc.description.sponsorshipThe project was funded by awards from the Medical Research Council MR/L010011/1, MR/K026666/1 and MR/L022974/1. We are grateful to Professor Sue Kimber for providing the Man12 hESC line used in these studies.en_US
dc.description.urihttps://www.doi.org/10.1007/s00204-017-1983-0en_US
dc.language.isoen_USen_US
dc.publisherSpringer Verlagen_US
dc.relation.ispartofArchives of Toxicology
dc.subjectApoptosisen_US
dc.subjectHepatocytesen_US
dc.subjectHuman developmenten_US
dc.subjectMaternal smokingen_US
dc.subjectNecrosisen_US
dc.subjectPluripotent stem cellsen_US
dc.titleModelling foetal exposure to maternal smoking using hepatoblasts from pluripotent stem cellsen_US
dc.typeArticleen_US
dc.identifier.doi10.1007/s00204-017-1983-0
dc.identifier.pmid28510779


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