title: Effects of in utero exposure of C57BL/6J mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin on epidermal permeability barrier development and function.
abstract: BACKGROUND
  Development of the epidermal permeability barrier (EPB) is essential for neonatal life. Defects in this barrier are found in many skin diseases such as atopic dermatitis.
  
  
  OBJECTIVE
  We investigated the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development and function of the EPB.
  
  
  METHODS
  Timed-pregnant C57BL/6J mice were gavaged with corn oil or TCDD (10 μg/kg body weight) on gestation day 12. Embryos were harvested on embryonic day (E) 15, E16, E17, and postnatal day (PND) 1.
  
  
  RESULTS
  A skin permeability assay showed that TCDD accelerated the development of the EPB, beginning at E15. This was accompanied by a significant decrease in transepidermal water loss (TEWL), enhanced stratification, and formation of the stratum corneum (SC). The levels of several ceramides were significantly increased at E15 and E16. PND1 histology revealed TCDD-induced acanthosis and epidermal hyperkeratosis. This was accompanied by disrupted epidermal tight junction (TJ) function, with increased dye leakage at the terminal claudin-1-staining TJs of the stratum granulosum. Because the animals did not have enhanced rates of TEWL, a commonly observed phenotype in animals with TJ defects, we performed tape-stripping. Removal of most of the SC resulted in a significant increase in TEWL in TCDD-exposed PND1 pups compared with their control group.
  
  
  CONCLUSIONS
  These findings demonstrate that in utero exposure to TCDD accelerates the formation of an abnormal EPB with leaky TJs, warranting further study of environmental exposures, epithelial TJ integrity, and atopic disease.
authors.affiliation: Department of Biological Sciences, and.
authors.forename: Clarisse S
authors.initials: CS
authors.lastname: Muenyi
authors.forename: Sandra Leon
authors.initials: SL
authors.lastname: Carrion
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Jones
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Kennedy
authors.forename: Andrzej T
authors.initials: AT
authors.lastname: Slominski
authors.forename: Carrie H
authors.initials: CH
authors.lastname: Sutter
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Sutter
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D015386:Hazardous Substances / Q000633:toxicity*; D007642:Keratosis; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D019108:Tight Junctions / Q000187:drug effects*; D014867:Water / Q000378:metabolism
chemical_list: D015386:Hazardous Substances; D000072317:Polychlorinated Dibenzodioxins; D014867:Water