title: Prenatal exposure to allergen, DNA methylation, and allergy in grandoffspring mice.
abstract: BACKGROUND
  Prenatal allergen exposure has been linked to both induction and protection of allergic sensitization in offspring. We hypothesized that prenatal exposure of mice (F0) to Aspergillus fumigatus (A. fumigatus) would be associated with decreased immunoglobulin (Ig) E and airway eosinophilia and alterations in CpG methylation of T-helper genes in third-generation mice (F2).
  
  
  METHODS
  Female BALB/c mice were sensitized to A. fumigatus (62.5, 125, 1250 μg, or saline) and re-exposed to the same dose on days 7 and 14 (early) or days 12 and 17 (late) gestation. Grandoffspring were treated with A. fumigatus (62.5 μg) at 9 weeks. IgE, IgG(1) , and IgG(2a) levels and cell counts from bronchoalveolar lavage fluid were determined. Lung DNA was pyrosequenced at multiple sites in the interferon (IFN)-γ and interleukin (IL)-4 promoters.
  
  
  RESULTS
  Grandoffspring of mothers dosed with 1250 μg early during pregnancy developed increased airway eosinophilia (P < 0.05). Grandoffspring of mothers dosed late in pregnancy developed lower IgE (P < 0.05) and airway eosinophilia (P < 0.05). Grandoffspring of mothers dosed early had lower methylation at IL-4 CpG(-408) and CpG(-393) compared to late dosed mice (P < 0.005 across all doses). Few correlations were found between methylation levels and airway eosinophilia and IgE.
  
  
  CONCLUSIONS
  Prenatal exposure to A. fumigatus late during pregnancy, but not early, was associated with lower IgE and airway eosinophilia in grandoffspring. Prenatal exposure to A. fumigatus was associated with changes in CpG methylation in the IFN-γ and IL-4 promoters that did not correlate consistently with indicators of allergic sensitization.
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Niedzwiecki
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: L
authors.initials: L
authors.lastname: Corson
authors.forename: G
authors.initials: G
authors.lastname: Grunig
authors.forename: P H
authors.initials: PH
authors.lastname: Factor
authors.forename: S
authors.initials: S
authors.lastname: Chu
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: R L
authors.initials: RL
authors.lastname: Miller
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000946:Antigens, Fungal / Q000008:administration & dosage / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology; D019175:DNA Methylation; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011401:Promoter Regions, Genetic
chemical_list: D000485:Allergens; D000946:Antigens, Fungal; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma