Prenatal exposure to tobacco smoke sex dependently influences methylation and mRNA levels of the Igf axis in lungs of mouse offspring

Karolin F Meyer, Susanne Krauss-Etschmann, Wierd Kooistra, Marjan Reinders-Luinge, Wim Timens, Lester Kobzik, Torsten Plösch, Machteld N Hylkema

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26 Citaten (Scopus)
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BACKGROUND: Prenatal smoke exposure is a risk factor for abnormal lung development and increased sex-dependent susceptibility for asthma and COPD. Birth cohort studies show genome wide DNA methylation changes in children from smoking mothers, but evidence for sex-dependent smoke-induced effects is limited. The insulin-like growth factor (IGF) system plays an important role in lung development. We hypothesized that prenatal exposure to smoke induces lasting changes in promoter methylation patterns of Igf1 and Igf1r, thus influencing transcriptional activity, and contributing to abnormal lung development.

METHOD: We measured and compared mRNA levels along with promoter methylation of Igf1 and Igf1r and their protein concentrations in lung tissue of 30-day-old mice which had been prenatally exposed to cigarette smoke (PSE) or filtered air (control). Body weight at 30 days after birth was measured as global indicator of normal development.

RESULTS: Female PSE mice showed lower mRNA levels of Igf1 and its receptor (Igf1: p = 0.05; Igf1r: p = 0.03). Furthermore, CpG site specific methylation changes were detected in Igf1r in a sex-dependent manner and the body weight of female offspring was reduced after prenatal exposure to smoke, while protein concentrations were unaffected.

CONCLUSION: Prenatal exposure to smoke induces a CpG-site specific loss of Igf1r promoter methylation, which can be associated with body weight. These findings highlight the sex-dependent and potentially detrimental effects of in utero smoke exposure on DNA methylation and Igf1 and Igf1r mRNA levels. The observations support a role for Igf1 and Igf1r in abnormal development.

Originele taal-2English
Pagina's (van-tot)L542-L555
Aantal pagina's14
TijdschriftAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Nummer van het tijdschrift4
Vroegere onlinedatum27-jan.-2017
StatusPublished - 5-apr.-2017

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