title: Nicotine Exposure During Pregnancy Results in Persistent Midline Epithelial Seam With Improper Palatal Fusion.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE; Department of Molecular Biology and Genetics, Canik Basari University, Samsun, Turkey;
authors.forename: Ferhat
authors.initials: F
authors.lastname: Ozturk
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE;
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sheldon
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE;
authors.forename: Janki
authors.initials: J
authors.lastname: Sharma
authors.affiliation: Department of Biology, Ankara Branch of Council of Forensic Medicine of Turkey, Ankara, Turkey.
authors.forename: Kemal Murat
authors.initials: KM
authors.lastname: Canturk
authors.affiliation: Department of Electrical and Computer Engineering, University of Nebraska - Lincoln, Lincoln, NE;
authors.forename: Hasan H
authors.initials: HH
authors.lastname: Otu
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE; anawshad@unmc.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Nawshad
mesh_terms: D000818:Animals; D002972:Cleft Palate / Q000196:embryology*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009538:Nicotine / Q000494:pharmacology*; D010159:Palate / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D011247:Pregnancy; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D012907:Smoking / Q000009:adverse effects; D050497:Stillbirth
chemical_list: D009538:Nicotine