<i>In Utero</i>Exposure to Second-Hand Smoke Aggravates the Response to Ovalbumin in Adult Mice

Xiao, Rui; Perveen, Zakia; Rouse, Rodney; Donne, Viviana Le; Paulsen, Daniel B.; Ambalavanan, Namasivayam; Penn, Arthur

doi:10.1165/rcmb.2013-0164oc

Cited by 24 publications

(38 citation statements)

References 38 publications

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“…We followed previously published procedures [20, 21, 23] for sectioning and staining 5-mm thick lung sections. We performed trichrome staining on 5-mm thick paraffin-embedded tissue sections.…”

Section: Methodsmentioning

confidence: 99%

Sex-specific lung functional changes in adult mice exposed only to second-hand smoke in utero

et al. 2017

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BackgroundAn increasing number of epidemiological and experimental studies have associated exposure to second-hand smoke (SHS) during pregnancy with adverse outcomes in newborns. As we have previously shown in mice, in utero exposure to SHS at critical stages of fetal development, results in altered lung responses and increased disease susceptibility upon re-exposure to irritants (SHS or ovalbumin) in adulthood. In this study, we asked whether the in utero SHS exposure alone is sufficient to alter lung structure and function in adult mice.MethodsPregnant BALB/c mice were exposed from days 6 to 19 of pregnancy to 10 mg/m3 of SHS or HEPA-filtered air. Male and female offspring (n = 13–15/group) were sacrificed at 15 weeks of age. We measured lung function with non-invasive and invasive methods, performed lung morphometric analysis on trichrome-stained lung tissue samples, and assessed lung gene expression via RNA sequencing and protein assays.Results In utero SHS exposure significantly increased mean linear intercept and decreased the surface area per unit volume of the lungs in both males and females, indicating perturbation in alveolar developmental processes. Tidal volume, minute volume and inspiratory capacity were significantly decreased compared with the controls only in male mice exposed in utero to SHS, suggesting that males are more sensitive than females to an SHS insult during lung development. This also suggests that in our model, lung structure changes may be necessary but are not sufficient to impair lung function. SERPINA1A, the mouse ortholog of human α1-antitrypsin, deficiency of which is a known genetic risk factor for emphysema, was down-regulated at the protein level in the in utero SHS-exposed mice. Additionally, DNMT3A protein expression was dysregulated, indicating that DNA methylation occurred in the lungs.ConclusionsOur results indicate that in utero SHS exposure alone alters both lung function and structure well into adulthood (15 weeks) in male mice. Furthermore, lung function alterations in this model are sex-specific, with males being more susceptible to in utero SHS effects. Overall, our data suggest that in utero SHS exposure alone can predispose to adult lung diseases.

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Section: Methodsmentioning

confidence: 99%

Sex-specific lung functional changes in adult mice exposed only to second-hand smoke in utero

et al. 2017

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“…Throughout the exposures, we recorded carbon monoxide (by infrared spectroscopy) and total suspended particulate (TSP) levels with a DustTrak and by gravimetric sampling. We selected a target TSP exposure level of 10 mg/m 3 , which has been previously used in in utero SHS-exposure studies (16)(17)(18). Various ambient parameters, including particle concentration, carbon monoxide content, temperature, and relative humidity (RH) were monitored daily for FA and SHS chambers during the entire 19 consecutive days (PND3-21) of 5 h/d exposures (Figs.…”

Section: Shs and Filtered Air Exposure Systemmentioning

confidence: 99%

Early Postnatal Secondhand Smoke Exposure Disrupts Bacterial Clearance and Abolishes Immune Responses in Muco-Obstructive Lung Disease

Lewis

Sultana

Sharma

et al. 2017

The Journal of Immunology

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Secondhand smoke (SHS) exposure has been linked to the worsening of ongoing lung diseases. However, whether SHS exposure affects the manifestation and natural history of imminent pediatric muco-obstructive airway diseases such as cystic fibrosis remains unclear. To address these questions, we exposed transgenic (-Tg) mice to SHS from postnatal day (PND) 3-21 and lung phenotypes were examined at PND22. Although a majority of filtered air (FA)-exposed -Tg (FA-Tg) mice successfully cleared spontaneous bacterial infections by PND22, the SHS-exposed -Tg (SHS-Tg) mice failed to resolve these infections. This defect was associated with suppressed antibacterial defenses, i.e., phagocyte recruitment, IgA secretion, and Muc5b expression. Whereas the FA-Tg mice exhibited marked mucus obstruction and responses, SHS-Tg mice displayed a dramatic suppression of these responses. Mechanistically, downregulated expression of IL-33, a stimulator of type II innate lymphoid cells, in lung epithelial cells was associated with suppression of neutrophil recruitment, IgA secretions, responses, and delayed bacterial clearance in SHS-Tg mice. Cessation of SHS exposure for 21 d restored previously suppressed responses, including phagocyte recruitment, IgA secretion, and mucous cell metaplasia. However, in contrast with FA-Tg mice, the SHS-Tg mice had pronounced epithelial necrosis, alveolar space consolidation, and lymphoid hyperplasia; indicating lagged unfavorable effects of early postnatal SHS exposure in later life. Collectively, our data show that early postnatal SHS exposure reversibly suppresses IL-33 levels in airspaces which, in turn, results in reduced neutrophil recruitment and diminished response. Our data indicate that household smoking may predispose neonates with muco-obstructive lung disease to bacterial exacerbations.

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“…The same four samples from each group with the highest quality (RIN range: 9.2-10.0) that were assessed initially via microarray (Xiao, et al, 2013) were assessed on an RNA-seq platform in the study. Library preparation begins with 1,000 ng of total RNA in 5 ml of nuclease-free water, to which is added an adapter oligonucleotide that is then ligated to the 3 0 hydroxyl present on miRNA species using T4 RNA Ligase (New England Biolabs).…”

Section: Rna Sequencing Analysis Mirnamentioning

confidence: 99%

“…Previously, we reported that in utero second-hand smoke (SHS) exposure aggravates adult responses to subsequent post-natal exposures to environmental irritants, including ovalbumin (OVA) Xiao et al, 2013] and SHS [Xiao et al, 2012]. In the most recent studies [Xiao et al, 2013], where we challenged all adult mice with OVA to induce allergic asthma, we found that the effects of in utero SHS exposure persisted into adulthood, further aggravated lung inflammation, elevated Th2 cytokine levels in bronchoalveolar lavage fluid (BALF), increased airway hyperresponsiveness (AHR), and altered gene expression profiles (microarray-based). However, whether in utero SHS dysregulates miRNA expression profiles and further modulates target gene expression in adult mice that have been challenged by OVA, remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

In utero exposure to second‐hand smoke activates pro‐asthmatic and oncogenic miRNAs in adult asthmatic mice

Xiao

Noël

Perveen

et al. 2016

Environ and Mol Mutagen

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Exposures to environmental pollutants contribute to dysregulated microRNA (miRNA) expression profiles, which have been implicated in various diseases. Previously, we reported aggravated asthmatic responses in ovalbumin (OVA)‐challenged adult mice that had been exposed in utero to second‐hand smoke (SHS). Whether in utero SHS exposure dysregulates miRNA expression patterns in the adult asthma model has not been investigated. Pregnant BALB/c mice were exposed (days 6–19 of pregnancy) to SHS (10 mg/m3) or HEPA‐filtered air. All offspring were sensitized and challenged with OVA (19–23 weeks) before sacrifice. RNA samples extracted from lung homogenates, were subjected to RNA sequencing (RNA‐seq). RNA‐seq identified nine miRNAs that were most significantly up‐regulated by in utero SHS exposure. Among these nine, miR‐155‐5p, miR‐21‐3p, and miR‐18a‐5p were also highly correlated with pro‐asthmatic Th2 cytokine levels in bronchoalveolar lavage fluid. Further analysis indicated that these up‐regulated miRNAs shared common chromosome locations, particularly Chr 11C, with pro‐asthmatic genes. These three miRNAs have also been characterized as oncogenic miRNAs (oncomirs). We cross‐referenced miRNA‐mRNA expression profiles and identified 16 tumor suppressor genes that were down‐regulated in the in utero‐exposed offspring and that are predicted targets of the up‐regulated oncomirs. In conclusion, in utero SHS exposure activates pro‐asthmatic genes and miRNAs, which colocalize at specific chromosome locations, in OVA‐challenged adult mice. The oncogenic characteristics of the miRNAs and putative miRNA‐mRNA regulatory networks suggest that the synergistic effect of in utero SHS exposure and certain adult irritants may promote an oncogenic milieu in mouse lungs via inhibition of miRNA‐regulated tumor suppressor genes. Environ. Mol. Mutagen. 57:190–199, 2016. © 2016 Wiley Periodicals, Inc.

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In UteroExposure to Second-Hand Smoke Aggravates the Response to Ovalbumin in Adult Mice

Cited by 24 publications

References 38 publications

Sex-specific lung functional changes in adult mice exposed only to second-hand smoke in utero

Sex-specific lung functional changes in adult mice exposed only to second-hand smoke in utero

Early Postnatal Secondhand Smoke Exposure Disrupts Bacterial Clearance and Abolishes Immune Responses in Muco-Obstructive Lung Disease

In utero exposure to second‐hand smoke activates pro‐asthmatic and oncogenic miRNAs in adult asthmatic mice

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