Generation of functional oocytes from male mice in vitro

Sex chromosome disorders severely compromise gametogenesis in both males and females. In oogenesis, the presence of an additional Y chromosome or the loss of an X chromosome disturbs the robust production of oocytes(1-5). Here we efficiently converted the XY chromosome set to XX without an additional Y chromosome in mouse pluripotent stem (PS) cells. In addition, this chromosomal alteration successfully eradicated trisomy 16, a model of Down's syndrome, in PS cells. Artificially produced euploid XX PS cells differentiated into mature oocytes in culture with similar efficiency to native XX PS cells. Using this method, we differentiated induced pluripotent stem cells from the tail of a sexually mature male mouse into fully potent oocytes, which gave rise to offspring after fertilization. This study provides insights that could ameliorate infertility caused by sex chromosome or autosomal disorders, and opens the possibility of bipaternal reproduction.

Automated summary

Sex chromosome disorders disrupt gametogenesis in both males and females. This study successfully converted the XY chromosome set to XX in mouse pluripotent stem cells and eliminated trisomy 16 associated with Down's syndrome. The artificially produced XX cells differentiated into mature oocytes and successfully resulted in offspring after fertilization. These findings have important implications for treating infertility caused by chromosomal disorders and offer the possibility of bipaternal reproduction.