Thesis Format
Monograph
Unfolding the Role of Endoplasmic Reticulum Stress and IRE1 Signaling in Trophoblast Differentiation
Degree
Master of Science
Program
Anatomy and Cell Biology
Collaborative Specialization
Developmental Biology
Supervisor
Renaud, Stephen J.
2nd Supervisor
Lajoie, Patrick
Co-Supervisor
Abstract
Impaired formation of a placental cell lineage called syncytiotrophoblast is associated with preeclampsia, a serious pregnancy complication. While endoplasmic reticulum stress and unfolded protein response (UPR) activation occur during healthy placentation, these processes are disrupted in preeclampsia. I hypothesize that activation of specific UPR branches is required for syncytialization and impaired UPR signaling disrupts syncytialization. I found that genes associated with UPR activation were upregulated during differentiation of BeWo cells, a model for studying syncytialization. I also found that inositol requiring enzyme 1 (IRE1) inactivation resulted in >50% reduction of cell fusion and human chorionic gonadotropin subunit β production. This impaired syncytialization was independent of classical spliced X-box binding protein 1 (XBP1s) and non-canonical c-jun NH2 terminal kinase (JNK) signaling pathways. My findings suggest that IRE1 branch signaling is required for syncytialization and could inform therapeutic approaches for preeclampsia through the modulation of UPR signaling.
Summary for Lay Audience
Preeclampsia is a dangerous pregnancy problem that is marked by high blood pressure and damaged blood vessels in the mom. In serious cases, preeclampsia can make the mom and baby very sick and sometimes they can die. Preeclampsia occurs when the placenta fails to form properly. The placenta is a temporary organ that forms during pregnancy to ensure that the baby gets the nutrients and oxygen it needs while in the womb. Since little is known about why the placenta does not form properly in preeclampsia, my research aims to understand more about the cells that make up the placenta. In placentas from preeclamptic pregnancies, placental cells are very stressed, and they do not function as well as they should. Cells activate a stress response mechanism to deal with the stress. Improper activation of the stress response mechanism could also be interfering with proper placental formation and may play a role in preeclampsia. In this study, I will investigate how inositol requiring enzyme 1 (IRE1), a protein involved in the stress response mechanism, contributes to placental formation. My results show that IRE1 is important for placental cells to form and function normally. By determining how stress response contributes to placental function and its potential role in preeclampsia, we can have a better understanding of why preeclampsia happens and develop better ways to prevent or treat this major problem.
Recommended Citation
Chowdhury, Diba, "Unfolding the Role of Endoplasmic Reticulum Stress and IRE1 Signaling in Trophoblast Differentiation" (2024). Electronic Thesis and Dissertation Repository. 10252.
https://ir.lib.uwo.ca/etd/10252
Creative Commons License
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