The aim of this project is to determine the functional role of NR5A1 (Steroidogenic factor-1, SF-1) in male gonadal development as well as its functional relevance to spermatogenesis in the adult male. Our lab has previously established the role SF-1 plays in fetal Leydig cell differentiation and development. Currently we aim is to understand the function of SF-1 in the development of Sertoli cell fetally as well as its adult testicular function in the maintenance of spermatogenesis. Steroidogenic Factor-1 is expressed in the both the fetal Sertoli cell as well as in the adult which makes the characterization of this gene product crucial for the understanding of testicular function. The phenotypic characteristics of the SF-1 null mouse shed light on the multiple levels at which this gene functions which includes the ventromedial hypothalamus, the pituitary, the ovary, testis and the adrenal. Mutation analysis of human patients soon followed and the findings showed that SF-1 played roles at multiple levels and that the severity spectrum from adrenal failure to male infertility differed in relation to different mutations. This severity spectrum is of particular interest to us with respect to male infertility due to the differential roles that this protein plays during development as well as for steady state spermatogenesis. In order to dissect these separate roles we have ablated the SF-1 gene specifically in the fetal Sertoli cells and have a strategy to ablate the gene in the differentiated Sertoli cell.
The outcome of this tissue specific knockout is the failure of Sertoli cells to develop and differentiate, resulting in apoptosis the secondary loss of germ cells. These preliminary studies strongly suggest that SF-1 gene is vital for the Sertoli cell survival during development. The loss of Sertoli cells prior to maturity precludes this knockout strategy for the study of this gene as it relates to spermatogenesis.Type your paragraph here.
Figure: Shows cell expression of sox9 in Sertoli cell specific knockout of SF-1 using AMH-Cre and loxed SF-1 mice. The red staining is BRDU and on the merge KO fetuses have very lttle overlap of Sox9 and BRDU showing a loss of proliferation. We also show high levels of tunel staining at E 15.5 after SF-1 ablation.