| Project/Area Number |
16591670
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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 | Nagasaki University |
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Principal Investigator |
MIURA Kiyonori Nagasaki University, Hospital of Medicine and Dentistry, Obstetrics and Gynecology, Assistant professor, 医学部・歯学部附属病院, 講師 (00363490)
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| Co-Investigator(Kenkyū-buntansha) |
MASUZAKI Hideaki Nagasaki University, Grande School of Biomedical Science, Obstetrics and Gynecology, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (00173740)
HIRAKI Koichi Nagasaki University, Hospital of Medicine and Dentistry, Obstetrics and Gynecology, Instructor, 医学部・歯学部附属病院, 助手 (30372775)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | placental mRNA / placental DNA / maternal plasma / real-time RT-PCR / H19 / methylation / genetic polymorphism / epigenetics / Confined placental mosaicism / DNA多型マーカー / matermal plasma / cord blood / maternal DNA |
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| Research Abstract |
The purpose of this project was to confirm the possibility of fetal DNA and mRNA in maternal plasma (cff-DNA and cff-mRNA) as novel molecular markers for monitoring an epigenetic status in placenta. Using cff-DNA and cff-mRNA, an expression status of placenta-specific expressed gene and/or an epigenetic status of imprinting gene was investigated.
1.Origin of cff-DNA and cff-mRNA in maternal plasma : The result of our study provides direct evidence for the release of placental DNA into the maternal circulation and suggests possible usefulness of such DNA for noninvasive prenatal diagnosis of genetic diseases and screening for placental dysfunction. Our results also provide strong evidence for trafficking of maternal cells into umbilical cord blood (UBC) during labor. Since such maternal DNA contamination may suggest the presence of microchimerism in UCB, the results also imply clinical importance of the use of cord blood at bone marrow transplantation. Latest our study showed that amnioc
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entesis did not affect on the concentration of cff mRNA flowing in maternal circulation, suggesting that the mechanisms of cff DNA and cff mRNA transfer into the maternal circulation are different.
2.Expression status of placenta specific expressed gene-clinical application as molecular markers-Placental mRNA in maternal plasma and its clinical application to the evaluation of the placental status in a pregnant woman with placenta previa-percreta : Real-time quantitative RT-PCR adopted in the present study could be used for a method sensitive enough to monitor changing mRNA levels resulting from apoptotic effects in the placenta, and consequently to evaluate invading conditions of the trophoblastic villus.
Clinical applications of plasma circulating mRNA analysis in cases of gestational trophoblastic disease (GTD) : Our results suggest that the measurement of plasma mRNA by real-time quantitative RT-PCR can be used as a non-invasive diagnostic, prognostic and follow-up test for GTD.
3.Methylation status of imprinting gene -possibility of novel molecular marker for epigenetic change in placenta- : We have provided another line of evidence that fetus-in-fetu is of monozygotic origin. This is the first case of FIF showing different methylation patterns between a host infant and fetiform mass. Our data of the methylation analysis will contribute to future studies on pathogenesis of FIF.
4.Microarray comparative genomic hybridization (CGH)-based prenatal diagnosis for chromosome abnormalities using cell-free fetal DNA in amniotic fluid : The results of the present study indicated that cffDNA in crude amniotic fluid can be used as a sample for microarray-CGH-based prenatal diagnosis of chromosome abnormality. The microarray-CGH with cffDNA provides a rapid and comprehensive analysis of copy-number genome changes. However, because of drawbacks of the method, it should be done in combination with conventional karyotyping. The cffDNA also exists in maternal circulation. If this technique is applied to the use of cff nucleic acids in the maternal plasma, it will become one of major non-invasive prenatal screening tests for fetal chromosome abnormalities and placental function. Less
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