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. CONCLUSION: 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.
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. CONCLUSION: 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: Caroline E W Herr; Rakesh Ghosh; Miroslav Dostal; Venuse Skokanova; Paul Ashwood; Michael Lipsett; Jesse P Joad; Kent E Pinkerton; Poh-Sin Yap; Joshua D Frost; Radim Sram; Irva Hertz-Picciotto Journal: Pediatr Allergy Immunol Date: 2011-02 Impact factor: 6.377
Authors: Elmar W Tobi; L H Lumey; Rudolf P Talens; Dennis Kremer; Hein Putter; Aryeh D Stein; P Eline Slagboom; Bastiaan T Heijmans Journal: Hum Mol Genet Date: 2009-08-04 Impact factor: 6.150
Authors: Bethany Winans; Anusha Nagari; Minho Chae; Christina M Post; Chia-I Ko; Alvaro Puga; W Lee Kraus; B Paige Lawrence Journal: J Immunol Date: 2015-03-25 Impact factor: 5.422
Authors: Robert Ys Cheng; Yan Shang; Nathachit Limjunyawong; Tyna Dao; Sandhya Das; Richard Rabold; James Sk Sham; Wayne Mitzner; Wan-Yee Tang Journal: Environ Mol Mutagen Date: 2014-01-21 Impact factor: 3.216
Authors: Rachel L Miller; Hanjie Zhang; Jacqueline Jezioro; Mariangels De Planell Saguer; Stephanie Lovinsky-Desir; Xinhua Liu; Matthew Perzanowski; Adnan Divjan; Wanda Phipatanakul; Elizabeth C Matsui Journal: Environ Res Date: 2017-04-26 Impact factor: 6.498