The influence of maternal nutrition on sex determination

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K17924
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental physiology(including physical medicine and nutritional physiology); Obstetrics and gynecology
• Research Institution: The University of Tokushima
• Principal Investigator: MIYAWAKI Shingo 徳島大学, 先端酵素学研究所(次世代), 特任助教 (70756759)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 性決定 / エピゲノム / ゲノム編集 / 代謝 / Sry

Outline of Final Research Achievements

Mammalian sex is determined by the expression of Sry in the fetal gonadal somatic cells (pre-Sertoli cells). We previously found that epigenetic regulation plays an important role on Sry regulation. The discovery of the fundamental role of epigenetic regulation of Sry led to a new research area, namely, on the mechanistic link between environmental cues and sex determination. Embryonic development may be influenced by the maternal nutritional and metabolic state as fetal environment. We speculate that the metabolism of fetal pre-Sertoli cells may influence their sex determination process.
We first compared the gene expression between pre-Sertoli cells and the other gonadal somatic cells at the sex-determining period. Gene ontology analysis showed that metabolism-related process is enriched in pre-Sertoli cells. To investigate the role of metabolic genes on sex determination, we generated knockout mice of these genes using CRISPR-Cas9 system and examined the effect on sex determination.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

生物が有性生殖を行うためのシステムである雌雄への性決定様式は多様であり、線虫や魚類、爬虫類などでは、環境に依存した栄養状態により雌雄の決まる種が存在する。これまで、哺乳類の性決定における環境と代謝に関する報告は世界的になく、本研究により初めて、哺乳類の性が環境による影響を受けることが示される。また、本研究は妊娠時の栄養管理に重要な知見を与え、ヒトの性分化疾患や胎仔発育異常の新たな原因及び疾患のメカニズムの解明に繋がると期待される。