While smoking has been on the decline, e-cigarette usage has been on the rise; especially in vulnerable populations, including pregnant women, who switch to e-cigarettes due to misperceptions regarding their safety. Furthermore, even though the contribution of traditional smoking to the pathogenesis of thrombotic diseases is well documented, the involvement of e-cigarettes in such disease processes remains unknown. Consequently, the present application outlines studies that address fundamental, mechanistic, epigenetic and clinically-relevant translational aspects of the adverse-health effects of in utero exposure to e-cigarettes, an increasingly popular form of tobacco, in the context of thrombotic disease and platelet biology, and in an e-liquid-, and sex-specific manner. These studies are of paramount significance given the “perceived safety” of e-cigarettes, and will be conducted using a novel/new whole body exposure model. The Aims of this proposal are: Aim 1. Investigate the impact of in utero e-cigarette exposure on platelet-dependent disease states. While there is compelling evidence that e-cigarettes do exert negative health effects, and that in utero exposure to tobacco contributes to thrombogenesis, whether e-cigarettes are associated with an increased risk of thrombotic diseases is yet to be determined. To address this issue, the consequences of in utero e- cigarette exposure on normal hemostasis and whether it participates in the development of thrombotic diseases will be determined. Subsequent studies will assess the impact of in utero e-cigarettes on clotting factors. Aim 2. Investigate the mechanism by which in utero e-cigarette exposure modulates platelet function. It is noteworthy that published data shows that e-cigarettes do enhance platelet function (e.g., aggregation) in adults. Nonetheless, it remains to be determined if in utero e-cigarettes produce similar effects or not. Thus, the overall goal of the experiments proposed in this section is to determine the mechanism and impact of in utero e-cigarette exposure on the various platelet functional responses, specific biochemical markers of platelet activation, pro- and anti-inflammatory, as well as on the platelet epigenetics. Collectively, these experiments will make major contributions to understanding the consequences of in utero exposure to e-cigarettes on platelet activation and cardiovascular human health, its epigenetics, and the mechanism by/through which they exerts these effects, in an e-liquid- and sex- specific manner.