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Developmental effects of tobacco smoke exposure during human embryonic stem cell differentiation are mediated through the transforming growth factor-? superfamily member, Nodal.

ABSTRACT: While the pathologies associated with in utero smoke exposure are well established, their underlying molecular mechanisms are incompletely understood. We differentiated human embryonic stem cells in the presence of physiological concentrations of tobacco smoke and nicotine. Using post hoc microarray analysis, quantitative PCR, and immunoblot analysis, we demonstrated that tobacco smoke has lineage- and stage-specific effects on human embryonic stem cell differentiation, through both nicotine-dependent and -independent pathways. We show that three major stem cell pluripotency/differentiation pathways, Notch, canonical Wnt, and transforming growth factor-?, are affected by smoke exposure, and that Nodal signaling through SMAD2 is specifically impacted by effects on Lefty1, Nodal, and FoxH1. These events are associated with upregulation of microRNA-302a, a post-transcriptional silencer of Lefty1. The described studies provide insight into the mechanisms by which tobacco smoke influences fetal development at the cellular level, and identify specific transcriptional, post-transcriptional, and signaling pathways by which this likely occurs.

SUBMITTER: Liszewski W

PROVIDER: S-EPMC3314096 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Developmental effects of tobacco smoke exposure during human embryonic stem cell differentiation are mediated through the transforming growth factor-β superfamily member, Nodal.

Liszewski Walter W Ritner Carissa C Aurigui Julian J Wong Sharon S Y SS Hussain Naveed N Krueger Winfried W Oncken Cheryl C Bernstein Harold S HS

Differentiation; research in biological diversity 20120228 4

While the pathologies associated with in utero smoke exposure are well established, their underlying molecular mechanisms are incompletely understood. We differentiated human embryonic stem cells in the presence of physiological concentrations of tobacco smoke and nicotine. Using post hoc microarray analysis, quantitative PCR, and immunoblot analysis, we demonstrated that tobacco smoke has lineage- and stage-specific effects on human embryonic stem cell differentiation, through both nicotine-dep ...[more]

PMID: 22381624

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Project description:BackgroundAirports may represent significant sources of secondhand smoke (SHS) exposure for both travelers and employees. While previously common smoking rooms have largely disappeared from US airports, smoking continues to occur outdoors at terminal entrances. SHS may be especially high at arrival areas, since they oftentimes are partially enclosed by overhead departures, creating stagnant microenvironments. This study assessed particulate matter <2.5 microns in diameter (PM2.5), a common surrogate for SHS, at airport terminal locations to evaluate both outdoor exposure risk and possible indoor drift of SHS from outdoor sources.MethodsA convenience sample of nine airport terminal arrival areas in the US state of Florida was surveyed between February and July 2018. PM2.5 levels were assessed outdoors and indoors at terminal entrances and at control areas far into terminal interiors. We also examined the impact of smoking location on SHS exposure by correlating cigarette and passing vehicle counts with PM2.5 levels at terminals with contrasting proximity of designated smoking locations to terminal entrances.ResultsAlthough outdoor PM2.5 levels (mean 17.9, SD 6.1 µg/m3) were significantly higher than indoors (p < 0.001), there was no difference between indoor areas directly inside terminal entrances and areas much further interior (mean 8.8, SD 2.6 vs mean 8.5, SD 3.0 µg/m3, p=0.49). However, when smoking areas were in close proximity to terminal entrances, the number of lit cigarettes and vehicular traffic per minute predicted 70% of the variance of PM2.5 levels (p < 0.001), which was attributable mostly to the cigarette number (β = 0.83; 95% CI (0.55 to 1.11); p < 0.001). This effect was not observed at smoking areas further away.ConclusionPM2.5 data did not suggest indoor drift from outside smoking. Nevertheless, absolute exposure outdoors was high and correlated with the location of designated smoking areas. Further studies are needed to examine the effect of microclimate formation on exposure risk.

Project description:The developing fetus is especially vulnerable to environmental toxicants, including tobacco constituents. The aim of this study was to assess the impact of environmental tobacco smoke (ETS) exposure during pregnancy on child neurodevelopment within the first two years of life. The study population consisted of 461 non-smoking pregnant women (saliva cotinine level <10 ng/mL). Maternal passive smoking was assessed based on the cotinine level in saliva analyzed by the use of high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-ESI + MS/MS) and by questionnaire data. The cotinine cut-off value for passive smoking was established at 1.5 ng/mL (sensitivity 63%, specificity 71%). Psychomotor development was assessed in children at the age of one- and two-years using the Bayley Scales of Infant and Toddler Development. Approximately 30% of the women were exposed to ETS during pregnancy. The multivariate linear regression model indicated that ETS exposure in the 1st and the 2nd trimesters of pregnancy were associated with decreasing child language functions at the age of one (? = -3.0, p = 0.03, and ? = -4.1, p = 0.008, respectively), and two years (? = -3.8, p = 0.05, and ? = -6.3, p = 0.005, respectively). A negative association was found for cotinine level ?1.5 ng/mL in the 2nd trimester of pregnancy and child cognition at the age of 2 (? = -4.6, p = 0.05), as well as cotinine levels ?1.5 ng/mL in all trimesters of pregnancy and child motor abilities at two years of age (? = -3.9, p = 0.06, ? = -5.3, p = 0.02, and ? = -4.2, p = 0.05, for the 1st, the 2nd, and the 3rd trimester of pregnancy, respectively; for the 1st trimester the effect was of borderline statistical significance). This study confirmed that ETS exposure during pregnancy can have a negative impact on child psychomotor development within the first two years of life and underscore the importance of public health interventions aiming at reducing this exposure.

Project description:BackgroundThirdhand smoke (THS) is the persistent residue resulting from secondhand smoke (SHS) that accumulates in dust, objects, and on surfaces in homes where tobacco has been used, and is reemitted into air. Very little is known about the extent to which THS contributes to children's overall tobacco smoke exposure (OTS) levels, defined as their combined THS and SHS exposure. Even less is known about the effect of OTS and THS on children's health. This project will examine how different home smoking behaviors contribute to THS and OTS and if levels of THS are associated with respiratory illnesses in nonsmoking children.MethodsThis project leverages the experimental design from an ongoing pediatric emergency department-based tobacco cessation trial of caregivers who smoke and their children (NIHR01HD083354). At baseline and follow-up, we will collect urine and handwipe samples from children and samples of dust and air from the homes of smokers who smoke indoors, have smoking bans or who have quit smoking. These samples will be analyzed to examine to what extent THS pollution at home contributes to OTS exposure over and above SHS and to what extent THS continues to persist and contribute to OTS in homes of smokers who have quit or have smoking bans. Targeted and nontargeted chemical analyses of home dust samples will explore which types of THS pollutants are present in homes. Electronic medical record review will examine if THS and OTS levels are associated with child respiratory illness. Additionally, a repository of child and environmental samples will be created.DiscussionThe results of this study will be crucial to help close gaps in our understanding of the types, quantity, and clinical effects of OTS, THS exposure, and THS pollutants in a unique sample of tobacco smoke-exposed ill children and their homes. The potential impact of these findings is substantial, as currently the level of risk in OTS attributable to THS is unknown. This research has the potential to change how we protect children from OTS, by recognizing that SHS and THS exposure needs to be addressed separately and jointly as sources of pollution and exposure.Trial registrationClinicalTrials.gov Identifier: NCT02531594 . Date of registration: August 24, 2015.

Dataset Information

Developmental effects of tobacco smoke exposure during human embryonic stem cell differentiation are mediated through the transforming growth factor-? superfamily member, Nodal.

Publications

Developmental effects of tobacco smoke exposure during human embryonic stem cell differentiation are mediated through the transforming growth factor-β superfamily member, Nodal.

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