A01 Projects & Leaders

We will elucidate the functional fluctuation and changes in chromosome-mediated regulation of oocytes throughout reproductive life. A key interest is on mechanisms that maintain chromosome integrity throughout the adult stages and its deterioration resulting in chromosome segregation errors, as well as individual chromosome features that facilitate errors. The study will contribute to development of techniques to prevent chromosome segregation errors.

The naked mole-rat (NMR) is the longest-living rodent (> 30 y) resistant to aging and age-related diseases (e.g., cancer), making it an attractive model to seek mechanisms to prevent aging and cancer. To investigate such mechanisms, we are developing reproductive engineering techniques for NMR. NMRs are eusocial rodents, and breeding in a colony is confined to one queen and a few kings, whereas others are suppressed of sexual maturation. Thus, reproductive activation in non-breeding females is a key to advance our research.

We will elucidate the mechanism of oocyte dormancy, which determines the reproductive lifespan of female mammals, through (1) understanding the transcription factor network sufficient for oocyte dormancy, (2) reconstituting the somatic cell environment necessary for oocyte dormancy, and understanding the functional interactions between oocytes and somatic cells, and (3) developing a live imaging system to visualize the dormant state of oocytes accompanied with the dynamics of non-membranous structures and organelles.

The aim of our study is to understand the mechanisms of quiescence and growth of primordial follicles, an finite reservoir of matured oocytes. To achieve this, we take advantage in vitro and in vivo live imaging techniques. We also develop fluorescent labeled mouse lines and methods for quantitative image analysis useful for live imaging.

Our research aims to investigate the changes in various metabolites and metabolic pathways throughout the lifespan and their impact on reproductive function. The provided image depicts the distribution of a specific metabolite (cyan) in the testis of a male mouse fetus, showing its enrichment in germ cells (red). We believe that identifying metabolites with such distinctive distributions in germ cells and understanding their roles are crucial steps towards controlling reproductive function through interventions in the nutritional environment.

Paternal epigenetic information is transmitted through sperm chromatin. Sperm epigenome can be altered by nutrient levels and cell metabolism during lifespan. It remains largely unknown how the changes in sperm epigenome are established in spermatogenesis. We will elucidate the epigenetic dynamics in germ cells triggered by metabolic alterations throughout reproductive life.

We will develop novel technologies for highly sensitive metabolome analysis that can be performed on a small number of cells (less than 1,000 cells). Since metabolites have a wide range of physical and chemical properties, from easily soluble (hydrophilic metabolites) to almost insoluble (lipids), we will develop a highly sensitive analytical method optimized for each metabolite group. Furthermore, by applying this technology to germ cell research, we will elucidate the entire picture of life time-dependent metabolic changes that have been difficult to understand.

We are working on the development of nanoLC-MS analytical method, by which highly sensitive analysis can be achieved from trace amount samples without antibodies. This technique enables to perform various rare sample analysis, reduce costs and save laboratory animals for experiment. In this project, we are challenging to comprehensive analysis of metabolic enzyme proteins in germ cells (100-1000 cells) isolated from mouse testis and ovary, aiming to elucidate the effect of metabolic regulation on reproductive lifespan.