Department of Physiology and Pharmacology, London, Ontario, Canada.
Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
J Cell Mol Med. 2022 Jun;26(11):3223-3234. doi: 10.1111/jcmm.17328. Epub 2022 May 6.
Maternal cigarette smoking is a risk factor for congenital heart defects (CHDs). Nicotine replacement therapies are often offered to pregnant women following failed attempts of smoking cessation. However, the impact of nicotine on embryonic heart development is not well understood. In the present study, the effects of maternal nicotine exposure (MNE) during pregnancy on foetal heart morphogenesis were studied. Adult female mice were treated with nicotine using subcutaneous osmotic pumps at 0.75 or 1.5 mg/kg/day and subsequently bred with male mice. Our results show that MNE dose-dependently increased CHDs in foetal mice. CHDs included atrial and ventricular septal defects, double outlet right ventricle, unguarded tricuspid orifice, hypoplastic left ventricle, thickened aortic and pulmonary valves, and ventricular hypertrophy. MNE also significantly reduced coronary artery size and vessel abundance in foetal hearts. Moreover, MNE resulted in higher levels of oxidative stress and altered the expression of key cardiogenic regulators in the developing heart. Nicotine exposure reduced epicardial-to-mesenchymal transition in foetal hearts. In conclusion, MNE induces CHDs and coronary artery malformation in mice. These findings provide insight into the adverse outcomes of foetuses by MNE during pregnancy.
母亲吸烟是先天性心脏病 (CHD) 的一个风险因素。尼古丁替代疗法通常在戒烟失败后提供给孕妇。然而，尼古丁对胚胎心脏发育的影响还不是很清楚。在本研究中，研究了孕期母亲尼古丁暴露 (MNE) 对胎儿心脏形态发生的影响。成年雌性小鼠通过皮下渗透泵以 0.75 或 1.5mg/kg/天的剂量接受尼古丁处理，然后与雄性小鼠交配。我们的结果表明，MNE 剂量依赖性地增加了胎儿小鼠的 CHD 发生率。CHD 包括房间隔和室间隔缺损、双出口右心室、三尖瓣无保护瓣、左心室发育不良、主动脉瓣和肺动脉瓣增厚、心室肥厚。MNE 还显著降低了胎儿心脏中的冠状动脉大小和血管丰度。此外，MNE 导致氧化应激水平升高，并改变了发育中心脏的关键心脏生成调节剂的表达。尼古丁暴露减少了胎儿心脏的心外膜到间质的转变。总之，MNE 可诱导小鼠 CHD 和冠状动脉畸形。这些发现为孕期 MNE 导致胎儿不良后果提供了深入了解。
