Sox3 IS IMPORTANT FOR THE INITIATION AND PROGRESSION OF EARLY SPERMATOGENESIS

Spermatogenesis is a tightly regulated process in which germ cells progress through a differentiation process starting with spermatogonial stem cells (SSCs) and undifferentiated spermatogonia and ending with mature spermatozoa. Spermatogenesis has been described as a process with three main phases: proliferation, meiosis and differentiation. In a normal mouse testis, neonatal germ cells, called gonocytes, migrate to the basement membrane of the testis cord, where they are engulfed by the Sertoli cells shortly after birth. Only a few gonocytes that line the testis cords maintain their stem cell properties, while others undergo spermatogonial differentiation. By post-natal day 10 (P10), the first meiotic phase is initiated and by P20 the first post-meiotic germ cells are visible. Spermatogenesis continues as the animal matures and by 8 weeks of age, specific germ cell associations synchronized within tubule cross-sections are visible. We recently developed a Sox3 knockout mouse model with impaired spermatogenesis. Sox3 is expressed within a subset of undifferentiated spermatogonia. The seminiferous tubules of the Sox3 C57BL/6 knockout contain very few germ cells by 2 weeks of age and a decrease in differentiating germ cells and meiotic cells in 12-week-old animals suggesting a delayed initiation of spermatogenesis. RT-PCR analyses comparing P5 through P10 wildtype and Sox3-knockout animals demonstrate a decrease in several genes essential for SSC initiation, maintenance and progression through the phases of spermatogenesis. Because of the specific localization of Sox3 expression within the undifferentiated germ cell population and the impact of Sox3 ablation on the testis, this mouse model will provide a better understanding of Sox3 in the early junctures of spermatogenesis. (poster)