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A study published in Human Reproduction looks at the effect of an e-cigarette flavorant on human embryonic stem cells.
Prof Oliver Jones, Professor of Chemistry, RMIT University, said:
“This is an interesting study, and a nice illustration that everything is a chemical and everything is potentially toxic at the right concentration – even things we might usually think of as natural and harmless, such as vanillin. This is not the first time that vanillin in vapes has been implicated in development issues, although previous work was done in frogs (1, 2). The keyword here, though, is ‘potentially’. While I can see why the authors conducted the experiment with cells, a group of cells in a Petri dish is not the same as a human embryo. Cells in a dish are bathed in chemicals, which is not the case for an embryo. We can’t be sure exposure would be anything like the same.
“The TRPV4 channel itself is one of a family of six related types of protein in the body that act like chemical sensors, responding to things like touch, warmth, and water pressure. The V stands for vanilloid. In chemistry, vanilloids are compounds containing a common structural feature called a vanillyl group and include vanillin and capsaicin, the compound responsible for the taste and ‘heat’ of chillies.
“The work does not prove a link between vaping and women having difficulty conceiving and/or miscarriages. However, given the potential consequences, I think avoiding vapes and vaping while pregnant or trying to become pregnant is sensible general advice”
References
1) Dickinson A.J.G. et al. (2022) E-liquids and vanillin flavoring disrupts retinoic acid signaling and causes craniofacial defects in Xenopus embryos. Dev Biol 481 14-29, https://www.sciencedirect.com/science/article/pii/S0012160621002116
2) Black J.E. et al. (2025) E-Cigarette and vanillin exposure disrupts cardiovascular development in Xenopus laevis. Birth Defects Res 117, e2535, https://onlinelibrary.wiley.com/doi/10.1002/bdr2.2535
Prof Jacob George, Professor of Cardiovascular Medicine, University of Dundee, said:
“This is a concerning pre-clinical finding that merits attention for future clinical research correlation. As this is research done on embryonic cells in a lab, it will need to be further clarified in human clinical trials as laboratory findings do not necessarily always translate into clinically relevant outcomes. Having said that, many researchers including myself have been calling for the limiting of flavours in vapes and for further research to be done on the impact of flavourings. Whilst nicotine-containing vapes are seen as a harm reduction measure compared to tobacco cigarettes, the presence of unregulated chemicals in flavourings is a concern that needs to be addressed.”
Prof Marian Knight, Professor of Maternal and Child Population Health, University of Oxford, said:
“It is important to recognise that, while in itself this lab study is well designed and carried out, the way in which cells were exposed to the vanillin is very different from how the cells of a developing embryo might come in contact with vanillin as a result of maternal vaping. Many of the effects observed were evident only at levels of the chemical unlikely to reach the developing foetus of a mother who vapes. There were, however, some observed effects at levels which may be found in maternal blood, hence the importance of considering information like this in any discussion around vapes in pregnancy. It is not possible to generalise findings from studies like this to absolute pregnancy risks, such as a risk of miscarriage.”
Prof Benedikt Berninger, Professor of Developmental Neurobiology at King’s College London, said:
“In this paper, the authors show that vanillin at concentrations that could likely reach the uterus in a mother’s womb when vaping can activate the TRPV4 receptor. This receptor is expressed on the surface of stem cells that can be found during very early stages of human development. These stem cells when in culture (embryonic stem cells) respond to vanillin by increasing a second messenger (free calcium ions) and activating gene expression that directs the stem cells towards a specific germ layer fate (endoderm). Normally, these stem cells (epiblast cells) would go on to generate all cell types that constitute an organism, but this must happen at the right time and place. The authors point out that there is a risk that when vaping, mothers may inadvertently prematurely alter the fate decisions of these cells such that the embryo no longer is viable and able to develop properly, leading to miscarriage – however, as they acknowledge, their evidence is still very speculative as it is based on a very simplified in vitro model and also a limited set of data. It is well possible that in a real embryo, since it is more complex, the behaviour of the cells is under a more robust control and hence they would not be so easily misdirected. Thus, further research is needed, not only to confirm the data presented here, which I think is still mandatory, but also to make sure that the conclusions and resulting warnings are indeed warranted. While this paper has provided a suggestive link, it does not give direct evidence for the link between vaping and difficulty in conceiving and miscarriages. While this paper has provided a suggestive link, it does not give direct evidence for the link between vaping and difficulty in conceiving and miscarriages.”
‘Nanomolar vanillin, an e-cigarette flavorant, appears to disrupt pluripotency and promote endodermal differentiation in human embryonic stem cells via TRPV4 activation’ by Shabnam Etemadi et al. was published in Human Reproduction at 00:05 UK time on Thursday 13th August.
DOI: https://doi.org/10.1093/humrep/deag126
Declared interests
Prof Oliver Jones: “I have no COI to declare”
Prof Jacob George: “No COI to declare”
Prof Marian Knight: “I led national surveillance of covid-19 in pregnancy and am a co-investigator on the SINEPOST study (https://www.bristol.ac.uk/translational-health-sciences/research/neurosciences/research/neurology/sinepost-study/) investigating neurodevelopmental outcomes in children after maternal covid-19 infection. I hold grants from NIHR, HQIP and UKRI.”
Prof Benedikt Berninger: “no conflict of interest”