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postgraduate thesis: The effects of perfluorooctane sulfonate on placenta : modulation of placental lipid homeostasis
Title | The effects of perfluorooctane sulfonate on placenta : modulation of placental lipid homeostasis |
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Authors | |
Issue Date | 2016 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Kor, E. D. A. [許穎達]. (2016). The effects of perfluorooctane sulfonate on placenta : modulation of placental lipid homeostasis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. |
Abstract | Pregnancy is a delicate process in which the fetus needs to receive the right amount of nutrients from the mother to sustain proper growth. The placenta plays a special role in this period by separating the fetus from the maternal environment and coordinate this nutrient transport. Lipids are essential for proper fetal development, and serve multiple purposes such as energy source, signaling molecules, and cellular components. Although lipids can freely cross the membrane layers of the placental barrier, the placenta has mechanisms of active transport in place to ensure sufficient amount of lipids are available to the fetus. In situations where sufficient lipid provision is unattainable, both immediate and long-term complications of the fetus would develop.
The presence of lipid transporters in the placenta suggests the possibility of modulation by foreign chemicals. Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant known to disrupt hepatic lipid homeostasis and associated with low birth weights, and therefore is a candidate that may alter placental lipid transport by modulating the same lipid transporters that is available in the liver. However, current knowledge of the effects of PFOS on the placenta is limited, let alone the possibility of it affecting placental lipid transport.
In light of these ideas, this project sets out to investigate the potential effects of PFOS on placenta and placental lipid transport. The aim is to provide an understanding in the areas of exposure, toxic effects, potential sensitive period, lipid transporter modulation, and lipid uptake effects of PFOS on the placenta. It is hypothesized that PFOS will influence placental transport of lipids through modulation of lipid transporters in the placenta.
This project is the first to show evidence of potential placental lipid-disrupting effect of PFOS. Enhanced fatty acid uptake was found in JAr choriocarcinoma cell culture while the expression of two genes in the fatty acid binding protein (FABP) family were enhanced in murine placenta. The enhanced lipid uptake from PFOS exposure is unlikely to be due to modulation of placental lipid transporters, but the ability of PFOS to alter lipid fluidity may possibly play a role. Moreover, PFOS displayed signs of multi-mode mechanism of cytotoxicity that points to endocrine disrupting and apoptotic effects, and a disproportional increase in tissue PFOS levels from increased exposure suggests the risk on the placenta is present. Overall, this project has contributed valuable insights on the subject matter for future developments. |
Degree | Doctor of Philosophy |
Subject | Placenta Lipids - Metabolism Organic compounds - Health aspects Persistent pollutants - Health aspects |
Dept/Program | Biological Sciences |
Persistent Identifier | http://hdl.handle.net/10722/238833 |
HKU Library Item ID | b5824312 |
DC Field | Value | Language |
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dc.contributor.author | Kor, Eng Dar, Alec | - |
dc.contributor.author | 許穎達 | - |
dc.date.accessioned | 2017-02-20T02:06:37Z | - |
dc.date.available | 2017-02-20T02:06:37Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Kor, E. D. A. [許穎達]. (2016). The effects of perfluorooctane sulfonate on placenta : modulation of placental lipid homeostasis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. | - |
dc.identifier.uri | http://hdl.handle.net/10722/238833 | - |
dc.description.abstract | Pregnancy is a delicate process in which the fetus needs to receive the right amount of nutrients from the mother to sustain proper growth. The placenta plays a special role in this period by separating the fetus from the maternal environment and coordinate this nutrient transport. Lipids are essential for proper fetal development, and serve multiple purposes such as energy source, signaling molecules, and cellular components. Although lipids can freely cross the membrane layers of the placental barrier, the placenta has mechanisms of active transport in place to ensure sufficient amount of lipids are available to the fetus. In situations where sufficient lipid provision is unattainable, both immediate and long-term complications of the fetus would develop. The presence of lipid transporters in the placenta suggests the possibility of modulation by foreign chemicals. Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant known to disrupt hepatic lipid homeostasis and associated with low birth weights, and therefore is a candidate that may alter placental lipid transport by modulating the same lipid transporters that is available in the liver. However, current knowledge of the effects of PFOS on the placenta is limited, let alone the possibility of it affecting placental lipid transport. In light of these ideas, this project sets out to investigate the potential effects of PFOS on placenta and placental lipid transport. The aim is to provide an understanding in the areas of exposure, toxic effects, potential sensitive period, lipid transporter modulation, and lipid uptake effects of PFOS on the placenta. It is hypothesized that PFOS will influence placental transport of lipids through modulation of lipid transporters in the placenta. This project is the first to show evidence of potential placental lipid-disrupting effect of PFOS. Enhanced fatty acid uptake was found in JAr choriocarcinoma cell culture while the expression of two genes in the fatty acid binding protein (FABP) family were enhanced in murine placenta. The enhanced lipid uptake from PFOS exposure is unlikely to be due to modulation of placental lipid transporters, but the ability of PFOS to alter lipid fluidity may possibly play a role. Moreover, PFOS displayed signs of multi-mode mechanism of cytotoxicity that points to endocrine disrupting and apoptotic effects, and a disproportional increase in tissue PFOS levels from increased exposure suggests the risk on the placenta is present. Overall, this project has contributed valuable insights on the subject matter for future developments. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.subject.lcsh | Placenta | - |
dc.subject.lcsh | Lipids - Metabolism | - |
dc.subject.lcsh | Organic compounds - Health aspects | - |
dc.subject.lcsh | Persistent pollutants - Health aspects | - |
dc.title | The effects of perfluorooctane sulfonate on placenta : modulation of placental lipid homeostasis | - |
dc.type | PG_Thesis | - |
dc.identifier.hkul | b5824312 | - |
dc.description.thesisname | Doctor of Philosophy | - |
dc.description.thesislevel | Doctoral | - |
dc.description.thesisdiscipline | Biological Sciences | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.mmsid | 991044001141403414 | - |