Identification of a germline-specific Stra8 activator for the regulation of de novo oogenesis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07427
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Josai International University
• Principal Investigator: Niikura Yuichi 城西国際大学, 薬学部, 准教授 (10615107)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: Stra8 / 卵新生 / 卵巣老化 / 不妊症 / 再生

Outline of Final Research Achievements

In this study, we focused on the transcription factor Stra8, which is involved in oogenesis, aiming to understand its regulation and the mechanisms behind ovarian aging. We attempted to identify proteins that bind to Stra8 and are essential for its transcriptional activity, particularly those whose expression changes with age. Traditional immunoprecipitation methods often cause protein dissociation, so we used a proximity-dependent biotin labeling approach. Although we successfully achieved biotin labeling in living cells, we could not establish optimal elution conditions for affinity purification using streptavidin beads. As a result, we were unable to isolate and identify the target proteins. Nevertheless, the successful biotin labeling in living cells marks significant progress. Future efforts will focus on overcoming the elution challenges to isolate and identify Stra8-interacting proteins, enhancing our understanding of oogenesis and ovarian aging.

Free Research Field

生殖医学

Academic Significance and Societal Importance of the Research Achievements

Stra8は卵子形成に必須な転写因子で、その活性を制御する化合物は不妊症治療薬の可能性がある。今回、Stra8に結合するタンパク質群を網羅的にビオチン標識することに成功した。これらのタンパク質には、卵新生のON/OFFを制御し、卵巣恒常性の維持に関わる分子が含まれていると推測される。現在、卵新生は、分子機序は不明でエビデンスが少なく、懐疑的に見られている。Stra8制御分子の同定は、卵新生の分子機序を解明するだけでなく、卵巣老化との関係を紐解き、加齢による妊娠力の低下を説明することに貢献する。本研究成果は未完成でありながら、分子機序解明につながる大きな一歩である。