Common Vape Flavoring Vanillin May Disrupt Early Embryo Development, Study Finds

Vanillin, a flavoring chemical used in e-cigarettes, may interfere with embryonic development in pregnant women who vape, according to a study led by UC Riverside (UCR). Published August 12 in the journal Human Reproduction, the findings help explain previously reported links between vaping, difficulty becoming pregnant, and miscarriage.

The study used human embryonic stem cells in the lab — similar to cells in embryos at about three weeks — not pregnant women, and the researchers say it cannot prove the same effects occur in real embryos. UCR professor Prue Talbot and stem cell biologist Shabnam Etemadi exposed the cells to nanomolar (low) and micromolar (high) vanillin concentrations, chosen because it is often used at high levels in e-cigarette fluids and likely binds a cell-surface channel, TRPV4.

Micromolar concentrations tended to kill the cells, while nanomolar concentrations caused them to lose pluripotency — the ability to become any cell type — and differentiate into endoderm, the tissue that forms the gut lining and respiratory tissue, rather than ectoderm or mesoderm, the other cell types an embryo needs. Talbot said the changes could be serious and might prevent normal embryo development: without ectoderm the nervous system would not form, and without mesoderm tissues including muscle would not develop properly.

Blocking TRPV4 with an antagonist or an antibody prevented vanillin from causing these effects, pointing to TRPV4 as the mechanism: nanomolar vanillin binds the channel, triggering a rapid calcium influx that leads to the loss of pluripotency. Talbot said women trying to conceive or who have had miscarriages should be cautious, and that physicians should advise against vaping during pregnancy.

The researchers previously found that menthol, another e-cigarette flavoring, contributed to respiratory disease in humans, and are now studying the synthetic cooling chemical WS-23 and how both menthol and WS-23 affect embryonic cell differentiation. The study did not estimate the effects of repeated or cumulative vanillin exposure over days, weeks, months or years.