摘要：Background: In an effort to decrease the rates of smoking conventional tobacco cigarettes, electronic cigarettes (e-cigarettes) have been proposed as an effective smoking cessation tool. However, little is known about their toxicological impacts. This is concerning given that e-cigarette use is perceived as less harmful than conventional tobacco cigarettes during pregnancy for both the mother and fetus. Objective: The goal of this study was to test the neurodevelopmental consequences of maternal e-cigarette use on adult offspring behavior and neuroimmune outcomes. Methods: Pregnant female CD-1 mice were randomly assigned to one of three treatment groups ( n = 8 – 10 per group ) and exposed daily to either filtered air, propylene glycol and vegetable glycerol (50:50 PG/VG vehicle), or to PG/VG with 16 mg / mL nicotine ( + Nic ). Whole-body exposures were carried out for 3 h/d, 7 d/week, from gestational day (GD)0.5 until GD17.5. Adult male and female offspring (8 weeks old) were assessed across a battery of behavioral assessments followed by region-specific quantification of brain cytokines using multiplex immunoassays. Results: Adult offspring of both sexes exposed to + Nic exhibited elevated locomotor activity in the elevated plus maze and altered stress-coping strategies in the forced swim task. Moreover, male and female offspring exposed to PG/VG with and without nicotine had a 5.2% lower object discrimination score in the novel object recognition task. In addition to differences in offspring behavior, maternal e-cigarette exposure with nicotine led to a reduction in interleukin (IL)-4 and interferon-gamma ( IFN γ ) in the diencephalon, as well as lower levels of hippocampal IFN γ (females only). E-cigarette exposure without nicotine resulted in a 2-fold increase of IL-6 in the cerebellum. Discussion: These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy.
