Intrauterine exposure to e-vapour disrupts metabolic and hepatic homeostasis in mice

Publication Type:
Thesis
Issue Date:
2021
Full metadata record
Smoking during pregnancy harms foetal development, predisposing the offspring to develop metabolic disorders during adulthood. Excessive reactive oxygen species within cigarette smoke contributes to many pathologies, affecting almost all human organs. However, little is known about the role of oxidative stress in the development of metabolic disorders due to in-utero cigarette smoke exposure. Among pregnant women, vaping has become increasingly popular due to perceived safety as a tobacco cigarette replacement or smoking cessation option. However, e-cigarette vapour also contains reactive oxygen species, derived from the breakdown of flavouring and carrier molecules during heating. Thus, it is essential to investigate the safety of e-cigarettes as a tobacco cigarette replacement among pregnant women. Therefore, using mouse models, we aimed to investigate, i) the role of oxidative stress on the development of metabolic disorders in adult mice from dams exposed to cigarette smoke during pregnancy; ii) the consequences of replacing tobacco cigarettes with e-cigarettes during pregnancy on the offspring’s metabolic profile; iii) the impacts of vaping during pregnancy on the offspring’s metabolic health. For aims 1 and 2, female mice were exposed to cigarette smoke from six weeks prior to pregnancy - throughout gestation and lactation – until weaning of the pups. For aim 1, a subset of the cigarette smoke-exposed mice were additionally supplemented with a mitochondrial-targeted antioxidant in the drinking water after mating. For aim 2, a subset of the cigarette smoke-exposed mice were instead exposed to nicotine-containing, tobacco flavoured e-cigarette vapour from mating until weaning of the offspring. For aim 3, female mice were either exposed to nicotine-free or nicotine-containing tobacco flavoured e-cigarette vapour from six weeks prior to pregnancy until weaning of the pups. Plasma and livers were collected from 13-week-old male pups. Intrauterine tobacco smoke exposure resulted in glucose intolerance, hepatic steatosis, and increased liver damage in the offspring. These changes were associated with increased mitochondrial oxidative stress and were reversed by a mitochondrial-targeted antioxidant. Some of these changes were also reversed when the cigarette smoke was replaced by e-cigarette vapour, which likely contains less reactive oxygen species. Furthermore, e-cigarette vapour is detrimental to foetal development, independent of nicotine. Therefore, e-cigarettes should not be used during pregnancy, irrespective of nicotine content. Overall, this body of work suggests that oxidative stress plays a role in the development of metabolic disorders in mice with intrauterine exposure to cigarette smoke or e-cigarette vapour.
Please use this identifier to cite or link to this item: