2007 Fiscal Year Final Research Report Summary
Research concerning Effects of Endocrine Disrupters on Development of Cleft Lip and/or Palate
| Project/Area Number |
18592209
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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 |
Surgical dentistry
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| Research Institution | Aichi Gakuin University |
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Principal Investigator |
NIIMI Teruyuki Aichi Gakuin University, School of Dentistry, Lecturer (60291762)
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| Co-Investigator(Kenkyū-buntansha) |
NATSUME Nagato Aichi-Gakuin University, School of Dentistry, Professor (90183532)
MINAMI Katsuhiro Aichi-Gakuin University, School of Dentistry, Lecturer (70346162)
INOUE Makoto Aichi-Gakuin University, Shcool of Pharmacy, Professor (50191888)
SASAKI Takuma Aichi-Gakuin University, School of Pharmacy, Professor (90109976)
TANAKA Motohiro Aichi-Gakuin University, School of Pharmacy, Associate Professor (60197481)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Bisphenol A / Cleft Lip / Congenital Abnormality / Prevention / Thymus Gland |
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| Research Abstract |
We have elucidated that estradiol, which is estrogen, and bisphenol A (BPA), which is endocrine disrupters, inhibit development of cleft lip and palate in A/J mouse strain, which spontaneously develop cleft lip and palate, and that their inhibitory actions describe an inverted U dose-characteristic curve.
1. Correlation between an estrogen receptor and retinoic acid receptor (RAR), which are deeply involved in a process of bone differentiation from mesenchymal stem cells, was studied in order to know mechanism of a BPA action of inhibiting cleft lip and/or palate development.
(1) In a study about an effect of BPA on development of RAR using osteoblastic MC3T3-E1 cells, BPA at a concentration of 10-10M and 10-5M had no effect on RAR development.
(2) BPA elevated the mRAN level of osteopontin, which is a target gene of RAR, and the action of BPA became the maximum at a concentration of 10-8M shown in an inverted U dose-characteristic curve. The result showed that the action of BPA may possibly be involved deeply in a signal through RAR.
2. In order to study correlation between BPA and a RAR ligand, and further, in order to aim at developing a preventive medicine for cleft lip and for palate, 95 kinds of galenicals with 70% ethanol extraction were examined fix finding a RAR ligand to replace an all-trans retinoic acid, which is also a RAR ligand but has a strong action and various side effects.
(1) Atractylodinol was identified as a RAR α ligand from Atractylis Rhizoma
(2) Eugenol and isoeugenol were isolated and identified from clove.
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