NELL2-mediated lumicrine signaling through OVCH2 is required for male fertility

Local control of sperm maturation Newly produced spermatozoa within the testis do not have fertilizing ability but become fully functional when they mature in the epididymis. The development of the epididymis itself is dependent on testicular factors arriving via luminal flow. Improper signaling between the testis and epididymis is hypothesized to result in male infertility. Kiyozumi et al. identified NELL2 as a testicular luminal protein that binds to its receptor, ROS1, on the luminal epididymis surface and induces epididymal differentiation (see the Perspective by Lord and Oatley). In turn, differentiated epididymis secretes a fertility-essential protease, ovochymase-2, to make spermatozoa fully mature and functional. Thus, testis-epididymis interorgan communication by this “lumicrine” regulation ensures mammalian reproduction. Science , this issue p. 1132 ; see also p. 1053