Vanillin, a common flavouring chemical in e-cigarettes, may disrupt the normal development of embryos in pregnant women who vape, according to a study published today (Thursday) in Human Reproduction, one of the world’s leading reproductive medicine journals. [1]
The finding explains how vaping may be linked to women having difficulty conceiving and to miscarriages.
As it is practically impossible and also unethical to study the effect of chemicals on pregnant women and their developing embryos, researchers instead investigated human embryonic stem cells, which are similar to those in human embryos at three weeks old, in a series of tests in the laboratory. They warn that, as their findings are from a laboratory study, they cannot decisively establish that the same effects would be seen in women and their embryos.
Prue Talbot, Professor of Grad Division in the Molecular Cell & Systems Biology department at the University of California Riverside, USA, who led the study, said: “There is little understanding of how vaping can affect developing embryos in pregnant women who use electronic cigarettes. So we undertook this study to determine if vanillin, a flavour chemical often used in e-cigarettes at high concentrations, could adversely affect the development of young embryos in humans. We wanted to understand how chemicals in vape aerosols can affect young human embryos and identify the type of harm that may occur.”
“We focused on vanillin because it is frequently used in e-cigarette fluids, it is often used at high concentrations, and because we knew that embryonic cells had a channel called TRPV4 on their surfaces that would likely bind with vanillin.”
Prof. Talbot and Dr Shabnam Etemadi, a stem cell biologist and computational scientist also at the University of California Riverside, exposed human embryonic stem cells in dishes in the laboratory to different concentrations of vanillin: nanomolar (low) concentrations, or micromolar (high) concentrations. They also exposed the stem cells to a TRPV4 antagonist (a substance that inhibits vanillin binding to TRPV4), an antibody that blocks the function of TRPV4, or vanillin combined with either the antagonist or the antibody.
Embryonic stem cells have the potential to differentiate into any type of cell. In normal embryonic development, they form three cell types: endoderm, ectoderm and mesoderm.
Prof. Talbot said: “We found that micromolar concentrations tended to kill the cells. Nanomolar concentrations caused cells to lose pluripotency, which is the ability to develop into all cell types. Vanillin also caused the stem cells to differentiate into endoderm, rather than ectoderm or mesoderm. The endoderm is an embryonic tissue that gives rise to the lining of the gut and respiratory tissues. These changes are potentially very serious and could prevent normal development of embryos.”
The effect of vanillin on the stem cells was blocked by the TRPV4 antagonist, which identified the TRPV4 channel as the route by which vanillin adversely affected the cells.
“Our data predict that nanomolar concentrations of vanillin may reach the embryo in pregnant women who vape,” said Prof. Talbot. “At nanomolar concentrations, vanillin binds to a channel called TRPV4 on the surface of embryonic cells allowing a rapid influx of calcium, a signalling molecule. Calcium in turn activates downstream events that result in loss of pluripotency and differentiation of embryonic stem cells into endoderm. In normal development, the embryonic stem cells would form three cell types: endoderm, ectoderm and mesoderm. In embryos lacking ectoderm, the nervous system would fail to develop. In embryos lacking mesoderm, many tissues, such as muscle, would fail to develop.
“Women do not necessarily know the chemicals in vape products. Our findings suggest they should be cautious and advised by physicians not to vape during pregnancy, especially if they are having trouble conceiving or experience miscarriages.
“Regulatory policies are generally based on data derived from adults or adult cells. However, the prenatal stages of development are usually the most sensitive to environmental chemicals. When establishing policies for e-cigarette use and distribution, it would be advisable to consider if and how the products harm the unborn. Regulatory agencies should consider mandatory ingredient disclosure on packaging for e-cigarettes.”
The researchers have already investigated menthol flavouring in e-cigarettes and found that it was a contributor to respiratory disease in humans. They are now studying WS-23, a synthetic coolant often used in e-cigarette products, and examining the effects of menthol and WS-23 on differentiation of embryonic cells.
In addition to the lab study being unable to show definitively that the same effects would happen in human embryos, the researchers point out that their study does not predict the effect of cumulative exposure to vanillin over days, weeks, months or years. The effect of long-term exposure could be higher.
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[1] “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 and Prue Talbot. Human Reproduction journal. doi: 10.1093/humrep/deag126
Human Reproduction
Experimental study
Cells
Nanomolar vanillin, an e-cigarette flavorant, appears to disrupt pluripotency and promote endodermal differentiation in human embryonic stem cells via TRPV4 activation
13-Aug-2026