During development, the testis must descend into the scrotum in order for normal spermatogenesis to occur; any perturbations to this event can result in testis malpositioning (cryptorchidism) – a common birth defect linked to infertility and testicular cancer. The transcription factor E2F1 is associated with cryptorchidism and infertily in mice and humans, but how it influences testicular descent and spermatogenesis is unclear. Now, Dolores Lamb and colleagues report that E2F1 regulates these events in mice by controlling WNT4 signalling. They first show that mice deficient for E2f1 exhibit cryptorchidism, defective spermatogenesis and infertility. Specifically, E2f1 deficiency disrupts germ cell development and function, leading to germ cell depletion. The researchers also demonstrate that cell cycle and Wnt-signalling genes are aberrantly expressed in E2f1-deficient mice; although WNT4 is almost undetectable in the testes of adult mice, it continues to be expressed in E2f1-deficient mice, suggesting that germ cell depletion in these mice is due to increased WNT4 levels. In line with this, the researchers show that mice lacking both Wnt4 and E2f1 in germ cells are fertile. Together, these findings indicate that germ cell maintenance requires E2F1-mediated repression of Wnt4, supporting a role for WNT4 in germ cell survival and highlighting that WNT4 modulation could be used as an approach to treat cryptorchidism and male infertility.
Falling into place: the role of E2F1 in testes development
Falling into place: the role of E2F1 in testes development. Development 1 January 2021; 148 (1): e148_e0102. doi:
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