X-gene functions in spermatogonia, and their role in idiopathic and sex chromosome aneuploidy associated infertility.

In mammals, females have two X chromosomes (XX) while males have an X and Y (XY). The presence of the Y determines male development. However, a mismatch of sex chromosome complement with phenotypic sex, sex chromosome aneuploidy causes infertility i.e. Klinefelter syndrome ('KS'; XXY), Turner syndrome (XO) and, Double-Y syndromes (XYY). These are the most common group of human aneuploidies. Sperm production in males relies on spermatogonial stem cells (SSCs) and occurs throughout their lifetime. The ability of SSCs to self-renew, and also differentiate to sperm is poorly understood. KS infertility in particular remains poorly characterized, and men with KS experience a block in SSCs development early in life. This loss of gonadal function has lifelong health implications. We have recently described unique X-gene activity during normal spermatogenesis, and specific expression in SSCs. We now wish to understand how perturbation of X-gene dosage in SSCs may cause infertility.