2005 Fiscal Year Final Research Report Summary
Placental dysfunction and maternal endothelial cell dysfunction in the pathogenesis of preeclampsia
| Project/Area Number |
16591666
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kyushu University |
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Principal Investigator |
TSUKIMORI Kiyomi Kyushu University, Kyushu University Hospital, OBGYN, Research Associate, 大学病院, 助手 (90253450)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Hitoo Kyushu University, Graduate School of Medical Sciences, OBGYN, Professor, 理事(教授) (40038766)
FUKUSHIMA Kotaro Kyushu University, Kyushu University Hospital, OBGYN, Research Associate, 大学病院, 助手 (40304779)
SONODA Kenzo Kyushu University, Kyushu University Hospital, OBGYN, Research Associate, 大学病院, 助手 (30294929)
YOSHIMURA Takazumi Kyushu University, Kyushu University Hospital, OBGYN, Research Associate, 大学病院, 助手 (30404081)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Preeclmusia / Placental dysfunction / Endothelial cell dysfunction / Neutrophil / Systemic inflammatory response |
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| Research Abstract |
The aim of this study was to clarify the relationship between placental abnormalities and the potential cellular mechanisms contributing to the maternal endothelial cell dysfunction in preeclampsia from the viewpoint of neutrophill-endothelial cell interaction.
Firstly, we investigated the effect of sera from women with preeclampsia on neutrophils. It was demonstrated that the sera from women with preeclampsia significantly enhance N-formyl-methionyl-leucyl-phenylalanine-induced superoxide production as compared to the sera of normal pregnant women, and that enhanced superoxide production of neutrophils induces the endothelial cell injury. In addition, sera from women with preeclampsia inhibited 3H-thymidine incorporation and reduced cellular viability of cultured trophoblasts. Gel permeation showed that the greatest growth-inhibitory activity corresponded to a molecular weight of 50 kDa. The serum enhanced activity to neutrophils was found in the same fraction of the placental cytotoxic activity.
Next, we investigated whether placental ischemia/hypoxia stimulates the production of maternal serum cytotoxic factor(s) using pregnant rats treated with the nitric oxide synthase inhibitor(L-NAME). In L-NAME treated pregnant rats, light microscopy showed that giant cells were decreased in number and spongiotrophoblast layers were degenerated compared to control pregnant rats. Maternal serum cytotoxic activity to placental trophoblasts was present in L-NAME treated pregnant rats. Elevated serum TNF-α levels and increased expression of TNF-α in placental trophoblasts were observed in L-NAME treated pregnant rats.
These findings suggest that placental ischemia/hypoxia stimulate the factor(s), such as inflammatory cytokines, that promote several forms of endothelial dysfunction in preeclampsia, and contribute to the substantial risks for developing this disorder during pregnancy
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