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Nicotine Exposure During Pregnancy Results in Persistent Midline Epithelial Seam With Improper Palatal Fusion.

ABSTRACT: Nonsyndromic cleft palate is a common birth defect (1:700) with a complex etiology involving both genetic and environmental risk factors. Nicotine, a major teratogen present in tobacco products, was shown to cause alterations and delays in the developing fetus.To demonstrate the postpartum effects of nicotine on palatal development, we delivered three different doses of nicotine (1.5, 3.0, and 4.5mg/kg/d) and sterile saline (control) into pregnant BALB/c mice throughout their entire pregnancy using subcutaneous micro-osmotic pump. Dams were allowed to deliver (~day 21 of pregnancy) and neonatal assessments (weight, length, nicotine levels) were conducted, and palatal tissues were harvested for morphological and molecular analyses, as well as transcriptional profiling using microarrays.Consistent administration of nicotine caused developmental retardation, still birth, low birth weight, and significant palatal size and shape abnormality and persistent midline epithelial seam in the pups. Through microarray analysis, we detected that 6232 genes were up-regulated and 6310 genes were down-regulated in nicotine-treated groups compared to the control. Moreover, 46% of the cleft palate-causing genes were found to be affected by nicotine exposure. Alterations of a subset of differentially expressed genes were illustrated with hierarchal clustering and a series of formal pathway analyses were performed using the bioinformatics tools.We concluded that nicotine exposure during pregnancy interferes with normal growth and development of the fetus, as well results in persistent midline epithelial seam with type B and C patterns of palatal fusion.Although there are several studies analyzing the genetic and environmental causes of palatal deformities, this study primarily shows the morphological and large-scale genomic outcomes of gestational nicotine exposure in neonatal mice palate.The previous version was incorrect. New authors Ali Nawshad, Hasan Otu, Janki Sharma, and Elizabeth Sheldon have been included in this version; the funding and acknowledgement sections have been updated accordingly; the article title, some text, and one supplementary data file have been edited; and the corresponding author has been changed. The original corresponding author regrets these earlier errors.

SUBMITTER: Ozturk F

PROVIDER: S-EPMC4900233 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Nicotine Exposure During Pregnancy Results in Persistent Midline Epithelial Seam With Improper Palatal Fusion.

Ozturk Ferhat F Sheldon Elizabeth E Sharma Janki J Canturk Kemal Murat KM Otu Hasan H HH Nawshad Ali A

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 20151006 5

<h4>Introduction</h4>Nonsyndromic cleft palate is a common birth defect (1:700) with a complex etiology involving both genetic and environmental risk factors. Nicotine, a major teratogen present in tobacco products, was shown to cause alterations and delays in the developing fetus.<h4>Methods</h4>To demonstrate the postpartum effects of nicotine on palatal development, we delivered three different doses of nicotine (1.5, 3.0, and 4.5mg/kg/d) and sterile saline (control) into pregnant BALB/c mice ...[more]

PMID: 26443016

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Project description:BACKGROUND AND AIMS:Smokers can regulate their nicotine intake by altering the number of cigarettes smoked per day (CPD) and their smoking intensity. The current study aimed to compare the utility of self-reported CPD, total nicotine equivalents (TNE) and urinary cotinine to estimate nicotine intake during pregnancy. DESIGN:Longitudinal smoking behavior and biomarker data were collected at early pregnancy, late pregnancy and at postpartum as part of a smoking cessation trial to examine voucher-based incentives for decreasing smoking. SETTING:Obstetric practices in Burlington, Vermont, United States. PARTICIPANTS:A subset of participants (n = 47) from the parent trial, recruited between December 2006 and June 2012, who provided a urine sample at each assessment during early pregnancy, late pregnancy and postpartum. MEASUREMENTS:Smoking was assessed using self-reported CPD, TNE, TNE/CPD and urinary cotinine. FINDINGS:Pregnant smokers reported smoking 10.4 CPD at early pregnancy, 7.2 CPD at late pregnancy (a 31% reduction at late pregnancy, P = 0.001) and 8.6 CPD at postpartum (a 19% increase from late pregnancy, P = 0.08). TNE exposure was 41% (P = 0.07) and 48% (P = 0.03) lower at early and late pregnancy, respectively, compared to postpartum. TNE/CPD was on average 167% higher at late pregnancy compared to early pregnancy (P = 0.01) and remained high at postpartum, where it was 111% higher compared to early pregnancy (P = 0.007). Uriniary cotinine underestimated nicotine intake by 55% during early pregnancy and by 65% during late pregnancy compared to postpartum (Pinteraction < 0.001); the underestimation was greater in slower (Pinteraction < 0.001) versus faster (Pinteraction = 0.04) nicotine metabolizers. CONCLUSIONS:Neither cigarettes smoked per day (CPD) nor cotinine provides an accurate estimate of nicotine exposure during pregnancy. CPD underestimates nicotine intake substantially due to under-reporting and/or higher intensity of smoking, while cotinine underestimates nicotine intake markedly due to accelerated nicotine (and cotinine) metabolism during pregnancy.

Project description:Background and aimsSmoking during pregnancy is strongly associated with negative pregnancy and perinatal outcomes. Some guidelines recommend nicotine replacement therapy (NRT) for smoking cessation during pregnancy, but adherence with NRT is generally poor and could be partially explained by nicotine-related safety concerns. We compared pregnant women's cotinine and nicotine exposures from smoking with those when they were abstinent from smoking and using NRT.DesignSystematic review with meta-analysis and narrative reporting. Twelve studies were included: in most, only one type of NRT was used. Seven were quality-assessed and judge of variable quality.SettingStudies from any setting that reported nicotine or cotinine levels when smoking and later when abstinent and using NRT.ParticipantsPregnant women who smoked and became abstinent but used NRT either in a cessation study or in a study investigating other impacts of NRT.MeasurementsWe quality-assessed longitudinal cohort studies using a modified version of the Newcastle-Ottawa scale. For meta-analysis, we used mean within-person differences in cotinine or nicotine levels when smoking and at later follow-up when abstinent and using NRT. Where such data were not available, we calculated differences in group mean levels and reported these narratively, indicating where data were not completely longitudinal.FindingsOf the 12 included studies, four cotinine-measuring studies (n = 83) were combined in a random effects meta-analysis; the pooled estimate for the mean difference (95% confidence intervals) in cotinine levels between when women were smoking and abstinent but using NRT was 75.3 (57.1 to 93.4) ng/ml (I2 = 42.1%, P = 0.11). Of eight narratively-described studies, six reported lower cotinine and/or nicotine levels when abstinent and using NRT; two had mixed findings, with higher levels when abstinent but using NRT reported from at least one assay time-point.ConclusionsPregnant women who use nicotine replacement therapy instead of smoking reduce their nicotine exposure.

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Nicotine Exposure During Pregnancy Results in Persistent Midline Epithelial Seam With Improper Palatal Fusion.

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Nicotine Exposure During Pregnancy Results in Persistent Midline Epithelial Seam With Improper Palatal Fusion.

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