Maternal fructose consumption differentially programs the allergic airway response in male and female mouse offspring.

Epidemiological studies describe a positive correlation between sugar consumption during pregnancy and the risk for atopic respiratory diseases in the progeny. In the present study we developed an experimental model to test whether the offspring born to and/or breastfed by mice exposed to liquid fructose would manifest changes in the allergic airway disease induced by sensitization and challenge with ovalbumin (OVA). Male mice born to mothers consuming fructose during pregnancy and/or lactation exhibited exacerbated infiltration of eosinophils and lymphocytes in the bronchoalveolar lavage (BAL) after challenge with OVA. Such changes were not detected in the female progeny. On the other hand, the OVA-challenged female progeny born to and breastfed by mothers consuming fructose exhibited higher concentrations of IL-4, IL-5 and TGF-β1 in the BAL and IgE in serum. Additional characteristics that were specifically programmed in the male progeny born to mothers exposed to fructose during pregnancy and lactation comprised increased BAL levels of IL-10, eosinophil infiltration in the lung parenchyma, lung collagen deposition and goblet cell numbers and ccl11, muc5b and receptor for advanced glycation endproducts expression in the lung. Altogether, our experimental approach reveals a previously undescribed causal relationship between maternal fructose consumption and changes in the allergic response in the offspring exposed to the OVA model. Such changes are sex-specific and while the female progeny exhibits higher IL-4, IL-5, TGF-β1 and IgE levels upon challenge with OVA, only the male offspring manifested exacerbated hallmarks of severe disease, including cellular infiltration, goblet cell hyperplasia, and collagen deposition.