2-B-P-051 〇平田 尚也¹、堀之内 孝広²、諫田 泰成¹ Naoya Hirata¹, Takahiro Horinouchi², Yasunari Kanda^{1 1}国衛研・薬理、²北海道大・院医・細胞薬理 ¹Div. Pharmacol., NIHS, ²Dept. Cellular Pharmacol., Grad. Med., Hokkaido Univ. In recent years, heated tobacco products (HTPs), which heat at a non-burning temperature and produce aerosols containing chemicals, have been widely used. HTPs have been reported to reduce levels of harmful chemicals, such as nicotine, tar and carbonyl compounds, compared with traditional burnt tobacco products, while epidemiological study revealed that HTP smoking may be associated with low birth weight (LBW) incidence. However, the underlying molecular mechanisms are incompletely understood. In this study, we investigated the effects of cigarette smoke extract (CSE) from HTPs on the endoderm differentiation of human induced pluripotent stem cells (iPSCs). We found that the HTP-CSE decreased the endoderm markers SOX17 and FOXA2 during endoderm differentiation of iPSCs. Next, we focused on the phosphorylation of Smad2, which is phosphorylated by activation of ALK4/7 during endoderm differentiation. The HTP-CSE inhibited the phosphorylation of Smad2 during endoderm differentiation. These results suggest that HTP-CSE disrupts endoderm differentiation of iPSCs via inhibition of Smad2 phosphorylation. Thus, HTPs during pregnancy might induce LBW and poor fetal organ growth via a delayed endoderm differentiation.