2004 Fiscal Year Final Research Report Summary
Research of endocrine regulation of the invasive potential and apoptosis extravillous trophoblasts
| Project/Area Number |
14370533
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kobe University |
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Principal Investigator |
MARUO Takeshi Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (60135811)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUO Hiroya Kobe University, School of Medicine, Professor, 医学部, 教授 (60229432)
NAKABAYASHI Koji Kobe University, Graduate School of Medicine, Assistant, 大学院・医学系研究科, 助手 (80362789)
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| Project Period (FY) |
2002 – 2004
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| Keywords | extravillous trophoblast / thyroid hormone / invasive potential / apoptosis / 細胞接着関連分子 |
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| Research Abstract |
The present study was conducted to determine whether T_3 receptor exists in early placental extravillous trophoblasts (EVTs) and evaluate the influence of T_3 on Fas/Fas ligand expression, caspase-3, and poly (ADP-ribose) polymerase (PARP) cleavage and apoptosis in cultured early placental EVTs. Early placental EVTs expressed a 212-bp c-erb Aβ1 transcript and the T_3 receptor protein and exhibited significant levels of apoptosis in culture. Treatment with T_3 reduced the expression of Fas and Fas ligand as well as cleavage of caspase-3 and PARP and suppressed apoptosis in cultured EVTs. These results demonstrate that T_3 receptor is present in early placental EVTs and that T_3 suppresses apoptosis by down-regulating the expression of Fas and Fas ligand. Furthermore, in order to investigate the possible role of T_3 in the regulation of EVT invasion to the decidua, we have examined whether T_3 affects EVT invasive potential and the expression of matrix metalloproteinase-2 (MMP-2), MMP-3, tissue inhibitor metalloproteinase-1, fetal fibronectin (FN), and integrin α_5β_1 in cultured early placental EVTs. Matrigel invasion assay demonstrated that the treatment with T_3 significantly increased the number of cell projections of cultured EVTs. RT-PCR analysis revealed that the treatment with T_3 increased the expression of MMP-2, MMP-3, fetal FN, and integrin α_5β_1 mRNA in cultured EVTs. Immunocytochemical and Western immunoblot analysis revealed that treatment with T_3 increased the expression of MMP-2 and MMP-3 in cultured EVTs. The present results suggest that T_3 (10^<-8>_M) may play a vital role in up-regulating the invasive potential of EVTs into the decidua.
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