E2F1 deficiency impairs murine spermatogenesis and augments testicular degeneration in SCP3-nullizygous mice

MicroRNA-449 and MicroRNA-34b/c Function Redundantly in Murine Testes by Targeting E2F Transcription Factor-Retinoblastoma Protein (E2F-pRb) Pathway

“…The mitotic phase of spermatogenesis requires the active E2F-pRb pathway as evidenced by the fact that E2F1 depletion causes highly reduced spermatogonial proliferation and marked testicular atrophy (54). However, upon the initiation of meiosis, activities of the E2F-pRb pathway appear to be down-regulated probably because this suppression allows male germ cells to exit from the mitotic cell cycle and to enter the meiotic program as suggested by several earlier studies (52,(55)(56)(57).…”

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

“…We assessed the contribution of the genetic background to the phenotype by breeding the animals to C57Bl/6J‐strain, which showed that genetic background had a strong influence on the severity and the time course of the phenotype associated with E2F1 loss. In the previous studies on the E2F1 −/− mice the testicular atrophy has been reported from the age of 3 months onwards (Field et al ., 1996; Yamasaki et al ., 1996; Hoja et al ., 2004). In contrast, in C57Bl/6 genetic background significant testicular atrophy occurred already at P20.…”

“…There were no alterations in the pH2AX staining pattern in the E2F1 −/− ‐testis at P40 compared with E2F1 +/+ , which indicated that increased DNA damage was not the source of the spermatocyte apoptosis. In addition, this shows that the initial meiotic DSB formation occurred normally, as impaired DSB formation commonly leads to a decreased pH2AX staining in the spermatocytes (Hoja et al ., 2004; Lam & Keeney, 2014). This suggested that despite having high E2F1 expression levels in the cell types undergoing meiotic DSB formation, E2f1 did not contribute to this process.…”

Expression of Itch in Sertoli cells is controlled via the interaction of E2F1/DP1 complex with E2F and GATA motif

“…17,18 Previous studies of using genetic models by knockout and overexpression of E2F1 in mice have suggested that E2F1 is an important transcriptional regulator for male reproduction. 15,16 Male mice lacking E2F1 displayed testicular atrophy with severe loss of spermatogonia, which indicates that E2F1 exerts a unique and indispensable role in spermatogenesis, 16 such as maintenance of the stem cell niche in the testis. It is apparent that some genes pertinent to spermatogenesis can only be regulated by E2F1, but not other E2F members, even though there are functional overlaps among E2F members.…”

“…Earlier studies have implicated the involvement of members of the E2F transcription factor family in various physiological functions including spermatogenesis. 13,15,16 This family of transcription factors is divided into transcriptional activator E2Fs (E2F1-3) and repressor E2Fs (E2F4-6). 17 In our studies, a significant reduction in promoter activity following mutation on the E2F motif of the 5'-flanking region of Itch gene thus illustrate that this E2F motif works with some transcriptional activators to drive Itch gene transcription.…”