Maintenance of the differentiated state and cell cycle exit in adult
Sertoli cells depends on tumor suppressor retinoblastoma protein (RB,
also known as RB1). We have previously shown that RB interacts with
transcription factor E2F3 in the mouse testis. Here, we investigated how
E2f3 contributes to adult Sertoli cell proliferation in a mouse model of Sertoli cell-specific knockout of Rb by crossing these mice with an E2f3 knockout mouse line. In the presence of intact RB, E2f3 was redundant in Sertoli cells. However, in the absence of RB, E2f3 is a key driver for cell cycle re-entry and loss of function in adult Sertoli cells. Knockout of E2f3 in Sertoli cells rescued the breakdown of Sertoli cell function associated with Rb
loss, prevented proliferation of adult Sertoli cells and restored
fertility of the mice. In summary, our results show that RB-mediated
repression of E2F3 is critical for the maintenance of cell cycle exit
and terminal differentiation in adult mouse Sertoli cells.