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Mechanisms of Human Placental Growth

  • Author / Creator
    Riddell, Meghan R
  • 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.

  • Subjects / Keywords
  • Graduation date
    2013-11
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3JD4PX8Q
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Department of Physiology
  • Supervisor / co-supervisor and their department(s)
    • Guilbert, Larry J (Medical Microbiology and Immunology
    • Davidge, Sandra T (Obstetrics and Gynecology/ Physiology)
  • Examining committee members and their departments
    • Thebaud, Bernard (Pediatrics/ Physiology)
    • Morrish, Donald (Medicine)
    • Nelson, D. Michael (Obstetrics and Gynecology)