The Role of Hypoxia on Pyruvate Kinase M2, mammalian Target of Rapamycin, Mitochondrial Function, and Cell Invasion in the Trophoblast

• Main Author: Kimball, Rebecca Lutz
• Format: Others
• Published: BYU ScholarsArchive 2016
• Subjects: placenta; pyruvate kinase M2 (PKM2); intrauterine growth restriction (IUGR); metabolism; mammalian target of rapamycin (mTOR); Cell and Developmental Biology; Physiology
• Online Access: https://scholarsarchive.byu.edu/etd/5723; https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=6722&context=etd

This thesis will be organized into two chapters discussing the role of hypoxia in the human placenta. The goal of this thesis is to characterize pyruvate kinase M2, mammalian target of rapamycin, mitochondrial function, and cell invasion in hypoxic conditions in the trophoblast. Understanding the mechanisms of placental metabolism can lead to further treatments for placental diseases. Chapter one covers the background of intrauterine growth restriction, hypoxia, placental metabolism, and pyruvate kinase M2 (PKM2). Little is currently understood about the role of the mitochondria in placental diseases. Expression of PKM2, trophoblast cell invasion, and mitochondrial function is shown to be inhibited by hypoxia. PKM2 inhibition decreases trophoblast cell invasion and nuclear expression of PKM2, but increases mitochondrial function. Studying how hypoxia affects the placenta during placental diseases can help clarify the mechanisms by which these diseases occur. Chapter two further characterizes the background of intrauterine growth restriction and hypoxia. It also covers the background of mammalian target of rapamycin. The objective of this chapter was to assess activated mTOR in the trophoblast in hypoxia. Decreased placental and fetal weights, as well as trophoblast cell invasion were observed in hypoxia. A decrease in the activation of mTOR was also found in the hypoxic placenta. This study could provide insight into the physiological relevance of the pathways and could be targeted to help alleviate placental diseases.