Degree
Master of Science
Program
Physiology and Pharmacology
Supervisor
Dr. Daniel B. Hardy
Abstract
Nicotine exposure during pregnancy leads to adverse health outcomes, including compromised placental development. Although the molecular mechanisms remain elusive, recent studies identified that endoplasmic reticulum (ER) stress may underlie poor placentation. Therefore, we were interested in investigating the effects of nicotine exposure on the ER stress response in the placenta. A well-established maternal nicotine exposure rat model and Rcho-1 trophoblast giant cell model were utilized to address the research questions. Maternal nicotine exposure in vivo led to elevated ER stress in association with impaired disulfide bond formation and hypoxia. Nicotine exposure in vitro further differentiated that ER stress may be augmented directly through nicotinic acetylcholine receptor activation and indirectly through nicotine-induced hypoxia. Moreover, we relieved nicotine-induced ER stress in Rcho-1 cells in vitro using Tauroursodeoxycholic acid. In conclusion, this thesis provides novel mechanistic insight and contributes to the development of innovative therapeutic approaches to ameliorate nicotine-induced injury in pregnancy.
Recommended Citation
Wong, Michael Ka Chun, "Characterization of the nicotine-induced endoplasmic reticulum stress response in the rat placenta in vivo and in vitro" (2015). Electronic Thesis and Dissertation Repository. 2997.
https://ir.lib.uwo.ca/etd/2997
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Developmental Biology Commons, Laboratory and Basic Science Research Commons, Medical Cell Biology Commons, Medical Molecular Biology Commons, Medical Physiology Commons, Medical Toxicology Commons, Reproductive and Urinary Physiology Commons