Sox8 and Sertoli-cell function.

SOX8 is a transcription factor that belongs to the SoxE group of high mobility group (HMG) superfamily of genes. As Sox8 is widely expressed during development, and has male-specific expression at the critical period for sex determination, it was initially hypothesized that its inactivation would result in abnormal sex determination. Though knockout males showed normal sexual development, they did however display a progressive seminiferous tubule failure and infertility. Young males could occasionally sire litters, though fecundity decreased with age in parallel with an increase in the degeneration and disorganization of the seminiferous epithelium. SOX8 is a product of the adult Sertoli cells. Sox8 knockout males showed a progressive dysregulation of the spermatogenic cycle, including sloughing of spermatocytes and round spermatids into the epididymis and spermiation failure. Sperm that did reach the epididymis showed an age-dependent decrease in both total and progressive motility in addition to overall number. We conclude that SOX8 transactivated genes have key roles in adult Sertoli-cell function and its elimination results in progressive male infertility.