Assessment of the impact of the disturbance in endo-and-xeno environment on the next-generation: study on the mechanism for sexual immaturity and developmental disorders and the preventive method

2021 Fiscal Year Final Research Report

• Project/Area Number: 17H00788
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental impact assessment
• Research Institution: Kyushu University
• Principal Investigator: Ishii Yuji 九州大学, 薬学研究院, 准教授 (90253468)
• Co-Investigator(Kenkyū-buntansha): 廣田 有子 九州大学, 薬学研究院, 助教 (50588259) ; 宮内 優 九州大学, 薬学研究院, 助教 (50799947)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: ダイオキシン / 次世代影響 / 黄体形成ホルモン / 成長ホルモン / プロラクチン

Outline of Final Research Achievements

In this study, we considered dioxins as a chemical substance capable of disturbing both the internal and external environments. We examined the adverse effects of dioxins evoked on the next generation by using pregnant rats and mice, aiming to develop a safe and efficient preventive method toward these substances’ undesirable effects. DAPL1 was identified as an important gene for reducing growth hormone at critical period. Then, Dapl1-deficient mice were constructed and are continuously being used for further research and characterization. We comprehensively investigated UGT in rats and mice, identified the major isoform involved in glucocorticoid conjugation. In addition, the hetero-knockout mice have been established. Further, we showed that lipoic acid-enriched diet until weaning is effective to improve sexual immaturity at puberty. Finally, with regards to prolactin’s decrease in the dams, we were also able to elucidate the decrease in milk yield for the second next generation.

Free Research Field

衛生薬学

Academic Significance and Societal Importance of the Research Achievements

本研究は、実験動物をモデルとして行われたものであり、比較的低用量であるが環境中レベルよりは高い濃度で実施され、ヒトと実験動物ではダイオキシンへの感受性に違いがあることには留意する必要があります。但し、ヒトでも環境からの低レベルダイオキシン等への暴露を免れることは難しく、生物学的半減期も長いことから基礎的研究として重要と考えます。内外環境の撹乱による次世代影響の機構とその予防法を構築することは、環境中の有害因子レベルの低減方法の構築を呼びかけることに加えて、性未成熟、発育障害さらには母体側の虐待への改善策を提起することになり、健康指針につながることが期待されます。