Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1016/j.jaci.2017.03.017
Title (Primary) Maternal phthalate exposure promotes allergic airway inflammation over 2 generations through epigenetic modifications
Author Jahreis, S.; Trump, S.; Bauer, M.; Bauer, T.; Thürmann, L.; Feltens, R.; Wang, Q.; Gu, L.; Grützmann, K.; Röder, S. ORCID logo ; Averbeck, M.; Weichenhan, D.; Plass, C.; Sack, U.; Borte, M.; Dubourg, V.; Schüürmann, G.; Simon, J.C.; von Bergen, M.; Hackermüller, J. ORCID logo ; Eils, R.; Lehmann, I.; Polte, T.
Source Titel Journal of Allergy and Clinical Immunology
Year 2018
Volume 141
Issue 2
Page From 741
Page To 753
Language englisch
Keywords airway inflammation, asthma, phthalates, epigenetics, T cells
UFZ wide themes RU3;


Prenatal and early postnatal exposures to environmental factors are considered responsible for the increasing prevalence of allergic diseases. Although there is some evidence for allergy-promoting effects in children due to exposure to plasticizers like phthalates, findings of previous studies are inconsistent and lack mechanistic information.


We investigated the effect of maternal phthalate exposure on asthma development in the subsequent generations and their underlying mechanisms including epigenetic alterations.


Phthalate metabolites were measured within the prospective mother-child cohort LINA and correlated with asthma development in the children. A murine trans-generational asthma model was used to identify involved pathways.


In LINA maternal urinary concentrations of mono-n-butyl phthalate, a metabolite of butyl benzyl phthalate (BBP), were associated with an increased asthma risk in the children. Using a murine trans-generational asthma model, we demonstrate a direct effect of BBP on asthma severity in the offspring with a persistently increased airway inflammation up to the F2 generation. This disease-promoting effect was mediated by a BBP-induced global DNA hypermethylation in CD4+ T cells of the offspring as treatment with a DNA demethylating agent alleviated exacerbation of allergic airway inflammation. 13 transcriptionally down-regulated genes linked to promoter or enhancer hypermethylation were identified. Among these, the GATA-3 repressor Zfpm1 emerged as a potential mediator of the enhanced susceptibility for Th2-driven allergic asthma.


These data provide strong evidence that maternal BBP exposure increases the risk for allergic airway inflammation in the offspring by modulating the expression of genes involved in Th2 differentiation via epigenetic alterations.

Persistent UFZ Identifier
Jahreis, S., Trump, S., Bauer, M., Bauer, T., Thürmann, L., Feltens, R., Wang, Q., Gu, L., Grützmann, K., Röder, S., Averbeck, M., Weichenhan, D., Plass, C., Sack, U., Borte, M., Dubourg, V., Schüürmann, G., Simon, J.C., von Bergen, M., Hackermüller, J., Eils, R., Lehmann, I., Polte, T. (2018):
Maternal phthalate exposure promotes allergic airway inflammation over 2 generations through epigenetic modifications
J. Allergy Clin. Immunol. 141 (2), 741 - 753 10.1016/j.jaci.2017.03.017