Your browser doesn't support javascript.
loading
Grandmaternal allergen sensitization reprograms epigenetic and airway responses to allergen in second-generation offspring.
Lebold, Katie M; Cook, Madeline; Pincus, Alexandra B; Nevonen, Kimberly A; Davis, Brett A; Carbone, Lucia; Calco, Gina N; Pierce, Aubrey B; Proskocil, Becky J; Fryer, Allison D; Jacoby, David B; Drake, Matthew G.
Afiliación
  • Lebold KM; Department of Emergency Medicine, Stanford University School of Medicine, Palo Alto, California, United States.
  • Cook M; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Oregon Health and Science University, Portland, Oregon, United States.
  • Pincus AB; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Oregon Health and Science University, Portland, Oregon, United States.
  • Nevonen KA; Knight Cardiovascular Institute Epigenetics Consortium, Oregon Health and Science University, Portland, Oregon, United States.
  • Davis BA; Knight Cardiovascular Institute Epigenetics Consortium, Oregon Health and Science University, Portland, Oregon, United States.
  • Carbone L; Knight Cardiovascular Institute Epigenetics Consortium, Oregon Health and Science University, Portland, Oregon, United States.
  • Calco GN; Department of Medicine, Oregon Health and Science University, Portland, Oregon, United States.
  • Pierce AB; Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, United States.
  • Proskocil BJ; Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon, United States.
  • Fryer AD; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Oregon Health and Science University, Portland, Oregon, United States.
  • Jacoby DB; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Oregon Health and Science University, Portland, Oregon, United States.
  • Drake MG; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Oregon Health and Science University, Portland, Oregon, United States.
Am J Physiol Lung Cell Mol Physiol ; 325(6): L776-L787, 2023 12 01.
Article en En | MEDLINE | ID: mdl-37814791
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 are 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 the 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 with 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.NEW & NOTEWORTHY Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. This study shows that maternal allergen exposure during pregnancy promotes unique epigenetic trajectories in second-generation offspring at baseline and in response to allergen sensitization, which is associated with the potentiation of airway hyperreactivity. These effects are one mechanism by which maternal asthma may influence the inheritance of asthma risk.
Asunto(s)
Palabras clave

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Efectos Tardíos de la Exposición Prenatal / Asma Límite: Animals / Female / Humans / Pregnancy Idioma: En Año: 2023 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Efectos Tardíos de la Exposición Prenatal / Asma Límite: Animals / Female / Humans / Pregnancy Idioma: En Año: 2023 Tipo del documento: Article