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- W4387472505 abstract "Asthma susceptibility is influenced by environmental, genetic and epigenetic factors. DNA methylation is one form of epigenetic modification that regulates gene expression and is both inherited and modified by environmental exposures throughout life. Prenatal development is a particularly vulnerable time period during which exposure to maternal asthma increases asthma risk in offspring. How maternal asthma affects DNA methylation in offspring, and what the consequences of differential methylation are in subsequent generations, is not fully known. In this study, we tested the effects of grandmaternal house dust mite (HDM) allergen sensitization during pregnancy on airway physiology and inflammation in HDM-sensitized and challenged second-generation mice. We also tested effects of grandmaternal HDM sensitization on tissue-specific DNA methylation in allergen-naïve and -sensitized second-generation mice. Descendants of both allergen- and vehicle-exposed grandmaternal founders exhibited airway hyperreactivity after HDM sensitization. However, grandmaternal allergen sensitization significantly potentiated airway hyperreactivity and altered the epigenomic trajectory in second-generation offspring after HDM sensitization compared to HDM-sensitized offspring from vehicle-exposed founders. As a result, biological processes and signaling pathways associated with epigenetic modifications were distinct between lineages. A targeted analysis of pathway-associated gene expression found that Smad3 was significantly dysregulated as a result of grandmaternal allergen sensitization. These data show that grandmaternal allergen exposure during pregnancy establishes a unique epigenetic trajectory that reprograms allergen responses in second-generation offspring and may contribute to asthma risk." @default.
- W4387472505 created "2023-10-11" @default.
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- W4387472505 date "2023-10-10" @default.
- W4387472505 modified "2023-10-16" @default.
- W4387472505 title "Grandmaternal allergen sensitization reprograms epigenetic and airway responses to allergen in second generation offspring" @default.
- W4387472505 doi "https://doi.org/10.1152/ajplung.00103.2023" @default.
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