E-Cigarette and Vanillin Exposure Disrupts Cardiovascular Development in Xenopus laevis

IF 1.6 4区医学 Q4 DEVELOPMENTAL BIOLOGY

Birth Defects Research Pub Date : 2025-09-26 DOI:10.1002/bdr2.2535

James E. Black III, Thomas O. Raymond, Amanda J. G. Dickinson

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Abstract

Introduction

Congenital heart defects (CHDs) are a leading cause of perinatal mortality, and maternal cigarette smoking is a well-established risk factor. In recent years, electronic cigarette (e-cigarette) use has surged, yet its safety during pregnancy remains poorly defined. Human epidemiologic studies have yielded inconsistent results, underscoring the need for complementary approaches. Developmental vertebrate models provide a cost-effective first-line strategy to identify potential risks. Here, we used the Xenopus laevis model to investigate the effects of e-cigarette aerosol extracts on cardiovascular development during embryogenesis.

Methods

Xenopus embryos were exposed during critical stages (20–40) to an aerosolized extract of a vanillin flavored e-liquid (e-cigAM-F), nicotine only, or vanillin. Transgenic lines (gata1:GFP for blood, flk1:GFP for vessels) and O-dianisidine staining assessed blood and vascular development. Cardiac structure was evaluated by microscopy and immunofluorescence (troponin T); ventricular area and heart rate were quantified. RT-qPCR and reanalysis of existing RNA-Seq data assessed expression changes in cardiac and hematopoietic genes.

Results

Embryos exposed to e-cigAM-F had decreased levels of hemoglobin subunits, gata1, and heme biosynthetic genes in craniofacial tissues after exposure. Blood delivery to the head was reduced, though blood remained near the heart. Vascular labeling indicated altered vessel organization but not gross loss of vasculature. Tadpoles exposed to e-cigAM-F had smaller ventricles and modestly reduced heart rate. Early cardiogenic transcripts were also suppressed. Vanillin, but not nicotine, exposure phenocopied the e-cigAM-F effects with respect to heart morphology.

Conclusions

Exposure to an aerosolized e-liquid (particularly its vanillin component) perturbs cardiovascular development in Xenopus, manifesting as reduced cranial blood flow, vascular abnormalities, smaller ventricles, and slower heart rate. These results implicate flavoring chemicals (rather than nicotine alone) in developmental cardiotoxicity, underscoring the need for mechanistic and mammalian model studies of inhaled e-liquid constituents.

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电子烟和香兰素暴露破坏非洲爪蟾心血管发育

先天性心脏缺陷（CHDs）是围产期死亡的主要原因，而母亲吸烟是一个公认的危险因素。近年来，电子烟的使用量激增，但其在怀孕期间的安全性仍不明确。人类流行病学研究产生了不一致的结果，强调需要采取补充方法。发育中的脊椎动物模型为识别潜在风险提供了一种具有成本效益的一线策略。本研究采用非洲爪蟾（Xenopus laevis）模型，研究电子烟气溶胶提取物对胚胎发育过程中心血管发育的影响。方法在关键阶段（20-40），将爪蟾胚胎暴露于香兰素味电子液体（e-cigAM-F）、纯尼古丁或香兰素的雾化提取物中。转基因系（gata1：血液GFP， flk1：血管GFP）和o -二苯胺染色评估血液和血管发育。通过显微镜和免疫荧光（肌钙蛋白T）评估心脏结构；测量心室面积和心率。RT-qPCR和现有RNA-Seq数据的再分析评估了心脏和造血基因的表达变化。结果e-cigAM-F暴露后，胚胎颅面组织血红蛋白亚基、gata1和血红素生物合成基因水平降低。输送到头部的血液减少了，但血液仍在心脏附近。血管标记表明血管组织改变，但没有血管系统的严重丧失。接触电子香烟f的蝌蚪的心室变小，心率略有降低。早期心源性转录本也受到抑制。暴露于香兰素，而不是尼古丁，在心脏形态方面表现出电子香烟- f效应。结论：暴露于雾化电子液体（尤其是其香兰素成分）会干扰爪蟾的心血管发育，表现为颅血流量减少、血管异常、心室变小和心率减慢。这些结果暗示了调味化学物质（而不是尼古丁单独）在发育性心脏毒性中，强调了吸入电子烟液体成分的机理和哺乳动物模型研究的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Birth Defects Research Medicine-Embryology

CiteScore

3.60

自引率

9.50%

发文量

153

期刊介绍： The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks. Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.