Role of myostatin signaling in human trophoblast cell invasion
department or school: Medicine, Faculty of
department or school: Obstetrics and Gynaecology, Department of
data provider: DSpace
degree campus: UBCV
creator: Ahmed, Faten
issued: 2024-01-31T08:00:00Z
issued: 2022
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Placental insufficiency disorders, including preeclampsia (PET), intrauterine growth restriction (IUGR) and preterm labor (PTL), are major obstetric complications that can have devastating effects on both the mother and the fetus. These syndromes share a common phenomenon of poor placental trophoblast cell invasion into the uterine tissue. To date there are no effective treatments for these illnesses. Placental invasion is controlled by many hormones and growth factors, among which the transforming growth factor (TGF)-β superfamily is a well-known regulator. Myostatin (MSTN) is a TGF-β superfamily member recognized for its important role in muscle growth control. Recently, MSTN was shown to be secreted and functioning in the placenta. In addition, MSTN serum and/or placental levels were found to be upregulated in common pregnancy complications including PET and IUGR. Yet, the role of MSTN in placental biology is poorly understood. In this study, I confirmed the positive effect of MSTN treatment on human trophoblast invasion and performed mRNA sequencing on control and MSTN-treated primary trophoblast cells (n=5). This analysis identified 610 differentially expressed genes (DEGs) with a false discovery rate <0.05, of which 380 were upregulated and 230 genes were downregulated. DEGs were highly enriched in epithelial mesenchymal transition (EMT) genes, among which serine protease inhibitor E2 (SERPINE2), plasminogen activator inhibitor-1 (PAI-1), SRY-Box Transcription Factor 4 (SOX4) and the cell adhesion molecule N-cadherin (N-Cad) were validated using RT-qPCR and Western blot. I then demonstrated that each of those genes was involved in MSTN-induced trophoblast cell invasion. Finally, I investigated the upstream signaling and found that MSTN induced upregulation of SERPINE2, PAI-1 and N-Cad via the canonical ALK4/5-SMAD2/3/4 signaling pathway. iv However, SMAD2 does not appear to be involved in MSTN-induced PAI-1 upregulation. In addition, SOX4 was involved in MSTN-…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/83548
note: ROLE OF MYOSTATIN SIGNALING IN HUMAN TROPHOBLAST CELL INVASION by Faten Ahmed MD Assiut School of Medicine, Assiut University, Egypt 2000 Doctoral degree in Obstetrics and Gynecology, Assiut University, Egypt 2014 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (REPRODUCTIVE AND DEVELOPMENTAL SCIENCES) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) December 2022 © Faten Ahmed, 2022 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Role of Myostatin Signaling in Human Trophoblast Cell Invasion submitted by Faten Ahmed in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Reproductive and Developmental Sciences Examining Committee: Dr. Peter C. K. Leung, Department of Obstetrics & Gynecology, UBC Supervisor Dr. Christian Klausen, Department of Obstetrics & Gynecology, UBC Supervisory Committee Member Dr. Michael Anglesio, Department of Obstetrics & Gynecology, UBC Supervisory Committee Member Dr. Michael Kobor, Department of Medical Genetics, UBC University Examiner Dr. Anthony Cheung, Department of Obstetrics & Gynecology, UBC University Examiner iii Abstract Placental insufficiency disorders, including preeclampsia (PET), intrauterine growth restriction (IUGR) and preterm labor (PTL), are major obstetric complications that can have devastating effects on both the mother and the fetus. These syndromes share a common phenomenon of poor placental trophoblast cell invasion into the uterine tissue. To date there are no effective treatments for these illnesses. Placental invasion is controlled by many hormones and growth factors, among which the transforming growth factor (TGF)-β superfamily is a well-known regulator. Myostatin (MSTN) is a TGF-β superfamily member recognized for its important role in muscle growth control. …
has type: Thesis/Dissertation
date issued: 2023-05
is shown at: 10.14288/1.0422930
language: eng
degree discipline: Reproductive and Developmental Sciences
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Leung, P. C. K.
type: Text
identifier URI: http://hdl.handle.net/2429/83548