Access Type
Open Access Dissertation
Date of Award
January 2024
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Physiology
First Advisor
Gil Mor
Abstract
The increase in environmental challenges and exposure to pollutants like benzene poses pressing concerns for reproductive health. This dissertation investigates the impact of benzene exposure during gestation on placental function, a key determinant for fetal development and pregnancy outcomes. Our work establishes that benzene exposure during pregnancy induces maternal immune activation, leading to increased rates of fetal resorptions, compromised fetal growth, and abnormal placental development. Intriguingly, we identify a sexual dimorphic response in male and female placentas to benzene exposure, attributable to inherent differences between male and female placental biology. On a molecular level, benzene is metabolized into hydroquinone in the body, which disrupts trophoblast invasion and migration by activating the aryl hydrocarbon receptor pathway. We elucidate that hydroquinone induced AhR activation suppresses Twist1, a critical transcription factor for trophoblast function, subsequently leading to the downregulation of Ifitm1, an essential regulator of extravillous trophoblast migration and invasion. Collectively, our findings suggest a critical AhR-Twist1-IFITM1 axis that is disrupted by benzene exposure. These results offer critical insights into the detrimental effects of environmental pollutants on reproductive health and underscore the urgency for comprehensive investigations on the influence of volatile organic compounds during gestation.
Recommended Citation
Maxwell, Anthony, "Benzene Exposure In Reproductive Biology: A Comprehensive Analysis Of Placental Response And Molecular Mechanisms In Trophoblast Function" (2024). Wayne State University Dissertations. 3975.
https://digitalcommons.wayne.edu/oa_dissertations/3975
