Etemadi Shabnam, Talbot Prue
Department of Bioengineering, University of California, Riverside, CA 92521, United States.
Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA 92521, United States.
Stem Cells Transl Med. 2025 Mar 18;14(3). doi: 10.1093/stcltm/szae099.
Many electronic cigarettes (ECs) contain high concentrations of menthol. The effect of menthol on human embryos in pregnant women who vape is not well understood. Human embryonic stem cells (hESCs) (an epiblast model) were used to test the hypothesis that 6.4-640 nM and 19.2-192 µM menthol, which activates TRP (transient-receptor-potential) channels, alters calcium homeostasis in embryos and adversely affects processes that are critical to gastrulation. Micromolar concentrations of menthol inhibited mitochondrial reductase activity in hESCs, an effect that was blocked by TRPA1 and TRPM8 inhibitors. Pulsatile exposure to menthol elevated intracellular calcium primarily by activating TRPA1 channels at nanomolar concentrations and TRPM8 channels at µM concentrations. nM menthol significantly inhibited colony growth by activating TRPA1 channels, while both TRPA1 and TRPM8 were activated by µM menthol. Inhibition of colony growth was attributed to cell death induced by menthol activation of TRPA1 and TRPM8 channels. nM menthol altered colony phenotype by increasing the major/minor axis ratio via TRPA1 and TRPM8 channels. Both nM and µM menthol induced alterations in hESC colony motility, an effect that was blocked only by the TRPM8 inhibitor. The menthol-induced increase in intracellular calcium adversely influenced growth, death, and migration, processes that are critical in gastrulation. Menthol concentrations that reach embryos in women who vape are high enough to activate TRPA1 and TRPM8 channels and perturbed calcium homeostasis. Pregnant women who vape likely expose their embryos to menthol concentrations that are harmful. These data could help prevent birth defects or embryo/fetal death.
许多电子烟含有高浓度薄荷醇。薄荷醇对吸电子烟孕妇体内人类胚胎的影响尚不清楚。人类胚胎干细胞（hESCs）（一种上胚层模型）被用于检验以下假设：激活瞬时受体电位（TRP）通道的6.4 - 640 nM和19.2 - 192 µM薄荷醇会改变胚胎中的钙稳态，并对原肠胚形成的关键过程产生不利影响。微摩尔浓度的薄荷醇抑制了hESCs中的线粒体还原酶活性，TRPA1和TRPM8抑制剂可阻断这一作用。脉冲式暴露于薄荷醇主要通过在纳摩尔浓度下激活TRPA1通道和在微摩尔浓度下激活TRPM8通道来升高细胞内钙水平。纳摩尔浓度的薄荷醇通过激活TRPA1通道显著抑制集落生长，而微摩尔浓度的薄荷醇同时激活TRPA1和TRPM8通道。集落生长的抑制归因于薄荷醇激活TRPA1和TRPM8通道诱导的细胞死亡。纳摩尔浓度的薄荷醇通过TRPA1和TRPM8通道增加长短轴比来改变集落表型。纳摩尔和微摩尔浓度的薄荷醇均诱导hESC集落运动性改变，这一作用仅被TRPM8抑制剂阻断。薄荷醇诱导的细胞内钙增加对生长、死亡和迁移产生不利影响，而这些过程在原肠胚形成中至关重要。吸电子烟女性体内到达胚胎的薄荷醇浓度足以激活TRPA1和TRPM8通道并扰乱钙稳态。吸电子烟的孕妇可能使其胚胎暴露于有害浓度的薄荷醇中。这些数据有助于预防出生缺陷或胚胎/胎儿死亡。
