Pathogenetic study of preeclampsia by using TXAS-null trophoblasts and its mouse models

• Main Authors: Chen-Hsiao Pai, 白振學
• Other Authors: Shu Rung Lin
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/36913980861230964840

碩士 === 中原大學 === 化學研究所 === 96 === Preeclampsia is a pregnancy-related disorder that mostly occurs during the second or third trimester. It is defined by three clinical symptoms including hypertension, proteinuria, and pathological edema. In pregnant women with preeclampsia, worse development of placenta may result in mild growth retardation of fetus, or in the most severe cases, will cause fetal and maternal death. Up to date, the pathological mechanism of preeclampsia remains unclear, and there are no defined biomarkers or methods for its diagnosis and prevention. According to previous studies, circulating TXA2 in preeclampsic women is higher than that of normal pregnant women. And higher level of TXA2 may induce thrombosis and hypertension in these patients. Thus, TXA2 is thought to be an important factor related to the development of preeclampsia and this thesis will focus on it. In this thesis, in order to create the mouse model of preeclampsia, wild type and TXAS knockout pregnant mice were fed with different concentration of NaCl (1.8%, 2.7% and 3.6%) in drinking water or L-NAME, the inhibitor of NO synthase. The effect of TXA2 on preeclampsia was observed by measuring the blood pressure, urinary protein, edema, placenta weight, fetal weight and fetal size in these pregnant mice. Several defects including decreased body weight, decreased placenta weight, decreased fetal size and weight and abnormal cell arrangement and structure of kidney were found in wild type mice feeding with 1.8% and 2.7% high salt water, but not in TXAS knockout mice. Both wild type and knockout pregnant mice were almost died by 3.6% high NaCl drinking. The results demonstrated that knockout mice were more resistant to high salt treatment, implying the possible roles of TXA2 on the development of maternal and fetal defects during high salt treatment. In the model of L-NAME treatment, reduced placenta weight, reduced fetal size and higher D14 urinary protein were observed in wild type mice, but not in knockout mice. Although these two models fail to induce clinical symptoms of preeclampsia and plasma sEng and sFlt-1 and placenta sections did not show any abnormality, there were still several defects found in the morphology of kidney, fetus and placenta. And knockout mice show relatively minor defects after these treatments. These results may conclude that the deficiency of TXA2 in TXAS knockout mice will result in a higher degree of resilience to develop the above defects when treating with high salt and L-NAME. On the other hand, when wild type and knockout trophoblast stem cells were treated with thioglycolic acid for one hour. Hypoxia were induced in both cell lines, but wild type trophoblast stem cells show relative higher viability than knockout cells, demonstrating the role of TXA2 on the viability of wild type trophoblast stem cells during hypoxia.