Females have two X chromosomes, while males have one X and one Y chromosome. The mismatch between sex-chromosome makeup and phenotypic sex leads to infertility. In vivo studies showed that sperm formation in mice is prohibited by presence of two X chromosomes, and requires two genes from the Y chromosome: Sry, which directs gonadal somatic cells to form a testis, and Eif2s3y, which functions in germ cells to promote spermatogonial development into haploid round spermatids. Sex reversed men with XX male (de la Chapelle) syndrome do not produce sperm because they have two X chromosomes and no Y chromosome. Using fibroblasts established from an XX male mouse model, we generated Eif2s3y-expressing induced pluripotent stem cells (iPSCs) that have lost one X chromosome. In vitro germline differentiation and subsequent testis transplantation of them would potentially allow us to create round spermatids, the reproductive potential of which will be tested by oocyte injection. This research will have relevance to overcoming infertility of XX males.