RANKL – A new regulator of testicular function

Infertility and testicular germ cell tumors (TGCTs) are frequent conditions affecting the health of young men worldwide. In this thesis, the expression of the RANKL signaling system and the implications of RANKL inhibition in the male gonads have been investigated through a translational approach.

This approach combines basic research, such as in vitro and ex vivo studies and findings from mouse models, with clinical studies. Overall, the main findings in this thesis include:

RANKL signaling regulates male reproductive function by influencing the interaction between germ and Sertoli cells.

RANKL, RANK, and OPG are expressed in GCNIS and TGCTs and inhibition of RANKL signaling suppresses tumor growth in seminoma-derived cells in vitro and in vivo or GCNIS tissue, but not in embryonal-carcinoma derived cells.

The response to denosumab depends on Sertoli cell capacity where high OPG expression indicates Sertoli cell dysfunction, and serum AMH can be used to identify the subgroup of infertile men, who may benefit from denosumab treatment.


Collectively, this thesis shows that RANKL signaling is active in the adult human testis, and that dysregulation of the signaling pathway have implications for male infertility and, to a lesser extent, TGCTs.​