Androgen Promotes Differentiation of Promyelocytic Leukemia Zinc Finger (PLZF)+ Spermatogonia pool via Indirect Regulatory Pattern

We examined a regulatory role of the AR during the process of spermatogenesis. Using a SSCs-Sertoli cells co-culture system, we demonstrated that androgen negatively regulated Plzf in SSCs that co-exist with Sertoli cells. In addition, we identified Gata2 as a target of AR in Sertoli cells, and subsequently observed that Wilms tumor 1 (WT1) and ß1-integrin as two putative intermediate molecules to transfer the differentiation signals to SSCs. This signal pathway was further verified using androgen pharmacological deprivation mice model. These results demonstrate a regulatory pattern of androgen in SSCs niche, that androgen turns off the stemness maintenance switch PLZF in undifferentiated spermatogonia populations to promote spermatogenesis in an indirect way via multiple steps of signal transduction.