Maternal diet during gestation affect prostatic tissue component in SHR/Izm offspring
| Project/Area Number |
20K18147
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 前立腺肥大症 / 胎生期栄養状態 / エピゲノム変化 / 低蛋白食 / 高脂肪食 / DNAメチル化 / SHR / 神経内分泌細胞 / 蛋白質制限食 / 母体栄養状態 |
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| Outline of Research at the Start |
前立腺肥大症(BPH)は有病率の高い疾患であるが、前立腺が組織学的に肥大する明確な機序は未だに不明である。我々はこれまで前立腺内の神経内分泌細胞(NE細胞)がBPH発症の一因であることを解明してきたが、このNE細胞は胎生期に最も豊富に存在するものの個体差が非常に大きいことが知られている。そこで我々は、母体栄養状態が胎生期におけるNE細胞のエピジェネティックな変化を介してBPHを引き起こすという仮説を立て、基礎的研究を行うこととした。
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| Outline of Final Research Achievements |
Purpose: We evaluated how maternal diet affect the prostate of their pups.
Methods: SHR/Izm female rats were randomly classified into 3groups, low-protein diet (LPD), standard diet (SD) and high-fat diet (HFD) group. They were fed only the specific diet during pregnancy. After delivery, all mothers and pups were fed the standard food. At 48 weeks of age, their prostate were removed. Ee evaluated the prostate by fluorescence imuunostaining and genetic analysis.
Result: Epithelial area increased in LPD group, and stromal area increased in HFD group compared with the other groups. Real time PCR showed high expression of transcription factor, apoptosis inhibitor in LPD group and high expression of toll-like receptor, transcription factor, TGF beta and EMT associated gene in HFD group. Pyrosequencing DNA methylation analysis of TGFβ pathway showed that TGFβ1, TGFβR1, and Smad3 were hypomethylated in each group, however, there was no significant differences.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究において、胎生期の栄養状態が48週齢の前立腺組成変化に関わる可能性が示唆され、その原因としては前立腺における細胞増生、炎症、リモデリングなどが関わる可能性が示唆された。胎生期の母体低栄養は前立腺上皮増加に、胎生期の母体肥満は前立腺間質増加をきたし、その背景には低栄養ではアポトーシス抑制因子が、母体肥満ではEMTの関与が示唆された。本研究の意義として、BPH発症のエピゲノム機構が明らかとなれば、現行のα1アドレナリン受容体やテストステロンに着目した治療と全く一線を画す治療戦略、リスク予測が可能となることが期待される。
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Report
(4 results)
Research Products
(3 results)
