Prenatal smoke effect on mouse offspring Igf1 promoter methylation from fetal stage to adulthood is organ and sex specific.
Zhijun ZengKarolin F MeyerKhosbayar LkhagvadorjWierd KooistraMarjan Reinders-LuingeXijin XuXia HuoJuan SongTorsten PlöschMachteld Nelly HylkemaPublished in: American journal of physiology. Lung cellular and molecular physiology (2020)
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 (IGF1) 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 2 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 with the fetal and neonatal stages. In addition, the PSE effect in the adult stage was more pronounced in the lung compared with the liver. For most CpG sites, an inverse correlation was found for promoter methylation and mRNA expression when the data of all three stages were combined. 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.
Keyphrases
- dna methylation
- genome wide
- gene expression
- early life
- growth hormone
- pi k akt
- pregnant women
- high fat diet
- healthcare
- birth weight
- type diabetes
- transcription factor
- case control
- cell proliferation
- adipose tissue
- young adults
- high resolution
- insulin resistance
- drug induced
- social media
- weight loss
- endothelial cells
- human health
- health information
- signaling pathway
- climate change