Establishment of methods to upregulate the number of primordial follicles by activation of autophagy to improve lifelong fertility in mammals
| Project/Area Number |
17K19316
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Veterinary medical science, Animal science, and related fields
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| Research Institution | Yamagata University |
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Principal Investigator |
Kimura Naoko 山形大学, 農学部, 教授 (70361277)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 原始卵胞 / オートファジー / 新生仔 / 卵巣 / 生殖能 / 生殖寿命 / 卵母細胞 |
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| Outline of Final Research Achievements |
In mice that received Tat-beclin 1 or Sulfasalazine by 54 h after birth, the primordial follicle numbers were increased by about 1.2 times, 1.1 times, respectively compared with the control group at 60 h. Especially in the 13 to 15 months old mice, the numbers of primordial follicles, the secondary follicles and graafian follicles in the Tat-bec.1 group were also significantly greater than that in the control group. The lifetime total number of offspring in the Tat-bec.1 group was at least 5 pups greater than that in control group, suggesting that the upregulated primordial follicles have a normal developmental potential.
We report that an enhancement in autophagy in neonatal mice during the follicle formation period accelerates follicle assembly by promoting oocyte survival. Consequently, the stockpile of primordial follicles expands, leading to an improvement in individual lifelong fertility. This approach could be effective in increasing reproductive ability in other animal species.
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| Academic Significance and Societal Importance of the Research Achievements |
胎生後期から新生仔初期の卵巣で進行する原始卵胞形成過程の分子機構は、解析手法の難しさや動物モデルが少ないなどから、十分な全容解明には至っていない。本研究の原始卵胞数の上方制御モデルでの解析から、小サイズシストの優勢卵母細胞数が増加することで、卵の生存性が向上し、原始卵胞数の増加に寄与することが示唆された点は、学術的意義と考えられた。
また新生仔期に、安全性が高いオートファジー誘導剤の投与により、生体レベルで原始卵胞数を上方制御することで、生涯生殖能の向上に繋がることを実証できた点は、産業動物や希少な雌動物資源の維持と増産の効率化を図る上で、根本的解決に繋がり得る成果と考えられた。
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Report
(4 results)
Research Products
(35 results)
