It is well known that maternal age causes severe fertility deficiencies especially after the age of 35. Age-related infertility attracts public interest because it limits women’s career plans. One of common causes of age-related infertility is defects in the structure of genomic DNA during meiosis, a process that produces gametes such as sperms and oocytes. Abnormal structure of genomic DNA is frequently observed in oocytes collected from older women for fertility treatments, suggesting that proper control of genomic DNA structure in meiosis is the central molecular entity for the infertility in ageing. In this research, we aim to study the molecular mechanism that ensures fertility by focusing on the spatial organization of genomic DNA throughout meiosis.

To determine the spatio-temporal organization of genomic DNA in meiosis, we have synchronously induced meiosis in fission yeast cells as a model organism. We applied genome-wide chromosome conformation capture (Hi-C) to the fission yeast cells at different stages of meiosis. With next generation sequencing, our Hi-C determined the spatial proximities of genomic DNA loci throughout the nucleus, providing large datasets of DNA-DNA interactions throughout meiosis. Bioinformatic analysis of the interaction datasets revealed global changes in genomic DNA structures throughout meiosis. Furthermore, we have reconstructed 3D models of genomic DNA structure using the polymer simulation in combination with our Hi-C datasets. These results shed light on the molecular basis to regulate the structure of genomic DNA for the faithful inheritance of the genetic information.

We also used female mice as a model of ageing infertility. To dissect the diversity of genomic DNA structure in aged oocytes, we developed the experimental procedure to visualize its structure under the microscope, followed by the determination of spatial organization of genomic DNA by Hi-C at the resolution of single oocyte. Comparing the number of oocytes collected from young and aged female mice, only a few oocytes were obtained from aged mice but many of them from young mice. In addition, our microscopic observation showed abnormal structures of genomic DNA in aged mice. We have started Hi-C analysis to determine the spatial organization of genomic DNA prepared from young and aged oocytes. We will use our experimental approach that we have developed with fission yeast to generate 3D models for normal and abnormal structure of the mouse genomic DNA in meiosis. Our study of genomic DNA structures in meiosis will contribute to the understanding of age-related abnormalities in the structure of genomic DNA and to future fertility treatments.