Prenatal smoke effect on mouse offspring Igf1 promoter methylation from fetal stage to adulthood is organ- and sex-specific

Zeng, Z., Meyer, K. F., Lkhagvadorj, K., Kooistra, W., Reinders-Luinge, M., Xu, X., Huo, X., Song, J., Plösch, T. & Hylkema, M. N., 8-Jan-2020, In : American Journal of Physiology - Lung Cellular and Molecular Physiology.

Research output: Contribution to journalArticleAcademicpeer-review

Prenatal smoke exposure (PSE) is associated with reduced birth weight, impaired fetal development and increased risk for diseases later in life. Changes in DNA methylation may be involved, as multiple large-scale epigenome wide association studies showed that PSE is robustly associated with DNA methylation changes in blood among offspring in early life. Insulin-like growth factor-1 (IGF-1) is important in growth, differentiation and repair processes after injury. However, no studies investigated the organ-specific persistence of PSE-induced methylation change of Igf1 into adulthood. Based on our previous studies on the PSE effect on Igf1 promoter methylation in fetal and neonatal mouse offspring, we now have extended our studies to adulthood. Our data show that basal Igf1 promoter methylation generally increased in the lung but decreased in the liver (except for two persistent CpG sites in both organs) across three different developmental stages. PSE changed Igf1 promoter methylation in all three developmental stages, which was organ and sex-specific. The PSE effect was less pronounced in adult offspring compared to the fetal and neonatal stages. In addition, the PSE effect in the adult stage was more pronounced in the lung compared to the liver. For most CpG sites, an inverse correlation was found for promoter methylation and mRNA expression when combining the data of all three stages. This was more prominent in the liver. Our findings provide additional evidence for sex- and organ-dependent prenatal programming which supports the developmental origins of health and disease (DOHaD) hypothesis.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Publication statusE-pub ahead of print - 8-Jan-2020

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