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Permanent link (DOI): https://doi.org/10.7939/R3JD4PX8Q
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Mechanisms of Human Placental Growth Open Access
- Other title
Intrauterine growth restriction
- Type of item
- Degree grantor
University of Alberta
- Author or creator
Riddell, Meghan R
- Supervisor and department
Davidge, Sandra T (Obstetrics and Gynecology/ Physiology)
Guilbert, Larry J (Medical Microbiology and Immunology
- Examining committee member and department
Morrish, Donald (Medicine)
Nelson, D. Michael (Obstetrics and Gynecology)
Thebaud, Bernard (Pediatrics/ Physiology)
Department of Physiology
- Date accepted
- Graduation date
Doctor of Philosophy
- Degree level
The placenta is an essential transitory fetal organ responsible for the key processes of nutrient, oxygen, and waste transfer between the mother and the fetus throughout gestation. Placental size is, importantly, known to correlate to fetal weight, and the malfunction and malformation of the placenta is associated with the common pregnancy complication intrauterine growth restriction (IUGR). IUGR affects ~10% of all pregnancies is defined as a fetus that fails to achieve its genetic growth potential. No curative therapies are currently available for IUGR and a potential target for the development of treatments would be to increase placental growth. Thus, this thesis focused on elucidating mechanisms of two key processes for placental growth: 1) differentiation of the syncytiotrophoblastic epithelium, and 2) extension of the placental blood vessels, or angiogenesis.
Trophoblast differentiation is an essential process in placental growth for the syncytiotrophoblast is a single giant, multinucleate cell, covering the entire surface of the placenta and it is maintained and expands only through differentiation. Previous publications have presented evidence that the initiation of the apoptotic cascade and the externalization of the membrane phospholipid, phosphatidylserine, are required for trophoblast differentiation. However, many of these studies are controversial and were conducted in cell lines. The studies presented in this thesis demonstrate with primary cells that both apoptosis and the externalization of phosphatidylserine have no role in trophoblast differentiation.
The remaining studies present the identification of a novel population of fibroblastic cells within the human placenta, fibrocyte-like cells, and the ability of these cells to induce placental angiogenesis in vitro. It is also demonstrated that fibrocyte-like cells from IUGR placentas have a reduced ability to stimulate in vitro angiogenesis and thus may contribute to the malformation of the placenta in the established condition.
In conclusion, the results presented in this thesis are an important contribution to the understanding of the mechanisms of trophoblast differentiation and placental angiogenesis therefore significantly contributing to our understanding of placental growth.
- Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
- Citation for previous publication
Riddell M.R., Winkler-Lowen B., and L.J. Guilbert. The contribution of Apoptosis-inducing factor (AIF) to villous trophoblast differentiation. Placenta 2012; 33(2): 88-93.Riddell M.R., Winkler-Lowen B., Chakrabarti S., Dunk C., Davidge S.T., Guilbert L.J. The characterization of fibrocytes-like cells: A novel fibroblastic cell of the human placenta. Placenta 2012; 33(3): 143-50.
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