UC Riverside

Cigarette smoke is a mixture of over 7000 toxic components with at least 69 smoke chemicals producing cancers, suggesting that smoking is harmful to smokers. More importantly, the World Health Organization has estimated that 10% of the world’s population is involuntarily exposed to environmental tobacco smoke, a number that does not include developing embryos. However, tobacco exposure during embryonic development is one of the risk factors for developing a congenital birth defect. An understudied, yet important abnormality caused by maternal smoking is the improper development of the embryonic skeleton, which can result in long-term burdens on the affected child and their family, creating a need for investigation that is addressed in this thesis.

Due to the difficulty in quitting smoking while pregnant, women often look to use harm reduction tobacco products (HRTPs) because they are perceived as a safer alternative in comparison to conventional cigarettes. These products include ultra-filtered cigarettes with reduced carcinogen content, and chewing tobacco, which omits exposure to harmful combustion products. However, there is a lack of investigation to reveal the molecular mechanisms involved in skeletal embryotoxicity induced by conventional and harm-reduction tobacco, the unraveling of which is another objective of this thesis.

In the process of this investigation, an in vitro model based on human embryonic stem cells was developed. These cells are the only currently available cell culture system, which mimics the development of the human embryo. As this thesis shows, their differentiation into osteoblasts in vitro can be used to study chemical toxicity and the molecular mechanisms thereof.