Generation of functional oocytes from male mice in vitro.

Sex chromosome disorder greatly compromises gametogenesis in both males and females. In oogenesis, the presence of a Y chromosome or the loss of an X chromosome disturbs the robust production of oocytes. In this study, we efficiently converted the XY chromosome set into two X chromosomes without an extra Y chromosome in mouse pluripotent stem cells (PSCs). In addition, this chromosomal alteration successfully eradicated trisomy 16 in PSCs, which is a model of Down syndrome. The artificially produced euploid XX PSCs differentiated into mature oocytes in culture as efficiently as native XX PSCs. Importantly, by this means, induced pluripotent stem cells (iPSCs) from the tail of a sexually mature male differentiated into fully potent oocytes, which gave rise to offspring after fertilization. This study provides insights that could lead to a cure for infertility caused by sex chromosome or autosomal disorders, and paves a way forward to bipaternal reproduction. Examination of transcriptomes in GV and MII oocytes derived from sex converted and native XX ESCs