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Research concerning Effects of Endocrine Disrupters on Development of Cleft Lip and/or Palate

Research Project

Project/Area Number 18592209
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionAichi Gakuin University

Principal Investigator

NIIMI Teruyuki  Aichi Gakuin University, School of Dentistry, Lecturer (60291762)

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)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥2,470,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsBisphenol A / Cleft Lip / Congenital Abnormality / Prevention / Thymus Gland
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.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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