Cytochrome P450 2A5 methylation and gene expression profile is organ-specific and affected by maternal smoking during pregnancy

Khosbayar Lkhagvadorj, Karolin F. Meyer, Laura P. Verweij, Zhijun Zeng, Torsten Plosch, Machteld Hylkema

Research output: Contribution to journalMeeting AbstractAcademic

Abstract

Background: Prenatal smoke exposure (PSE) is a risk factor for COPD. One susceptibility gene for COPD is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine and nicotine clearance in the liver. Higher CYP2A6 activity is associated nicotine dependence. However, no research has addressed the PSE effects on CYP2A6, or CYP2A5 in the mouse.

Aim: To investigate the PSE effect on Cyp2a5 gene expression and promoter methylation in fetal and neonatal offspring.

Methods: C57BL/6 mice were exposed to fresh air or smoke from 3 weeks before conception until delivery. From liver and lung tissue, DNA and RNA were isolated for gene expression and promoter methylation analysis of Cyp2a5 in fetuses (E17.5) and neonates (D3).

Results: Cyp2a5 mRNA expression was increased in male neonatal liver from PSE offspring. In contrast, in the lung, Cyp2a5 expression was reduced in both fetal and neonatal male PSE offspring. Promoter methylation was sex-dependently induced in both fetal and neonatal liver from PSE offspring when compared to their corresponding control groups. In the fetal lung, methylation was downregulated by PSE. Promoter methylation of several CpG sites (inversely) correlated with mRNA expression in liver and lung in both fetal and neonatal offspring.

Conclusions: This study presents a PSE effect on Cyp2a5 expression, which is opposite in liver and lung and associated with promoter methylation. Induced Cyp2a5 gene expression in the neonatal liver may indicate a higher nicotine metabolism which, when translated to the human situation, could lead to an increased risk for COPD and higher nicotine dependence later in life.
Original languageEnglish
Number of pages2
JournalEuropean Respiratory Journal
Volume52
Issue numberSuppl.62
DOIs
Publication statusPublished - 15-Sep-2018
Event28th International Congress of the European-Respiratory-Society (ERS) - Paris, France
Duration: 15-Sep-201819-Sep-2018

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