Vanillin flavouring in vapes may disrupt embryo development

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 in the journal Human Reproduction. The research indicates that vaping may be linked to difficulty with conception as well as miscarriage.

As explained by study leader Professor Prue Talbot, from the University of California, Riverside, “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 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.”

As it is practically impossible and also unethical to study the effect of chemicals on pregnant women and their developing embryos, the researchers instead investigated human embryonic stem cells, which are similar to those in human embryos at three weeks old. Embryonic stem cells have the potential to differentiate into any type of cell.

Along with colleague Dr Shabnam Etemadi, Talbot exposed human embryonic stem cells in laboratory dishes to either nanomolar (low) concentrations or micromolar (high) concentrations of vanillin. 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.

While micromolar concentrations tended to kill the cells, Talbot noted that nanomolar concentrations caused cells to lose pluripotency, which is the ability to develop into all cell types. Furthermore, the team’s data predicted that nanomolar concentrations of vanillin may reach the embryo in pregnant women who vape.

“At nanomolar concentrations, vanillin binds to … TRPV4 on the surface of embryonic cells allowing a rapid influx of calcium, a signalling molecule,” Talbot said. “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.”

The researchers said the effect of vanillin on the stem cells was blocked by the TRPV4 antagonist, thus identifying the TRPV4 channel as the route by which vanillin adversely affected the cells. They further stated that their work does not predict the effect of cumulative exposure to vanillin over days, weeks, months or years, so the effect of long-term exposure could be higher. That said, as their findings are from a laboratory study, they cannot decisively establish that the same effects would be seen in women and their embryos.

Nevertheless, Talbot concluded that women “should be cautious and advised by physicians not to vape during pregnancy, especially if they are having trouble conceiving or experience miscarriages”.

“When establishing policies for e-cigarette use and distribution, it would be advisable to consider if and how the products harm the unborn,” she added. “Regulatory agencies should consider mandatory ingredient disclosure on packaging for e-cigarettes.”

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