Ca²⁺ signaling tools acquired from prostasomes are required for progesterone-induced sperm motility

Progesterone-induced calcium ion (Ca²⁺) signals in the neck region of sperm play a pivotal role in promoting sperm motility. Here, we show that a long-lasting Ca²⁺ signal required for sperm motility in response to progesterone depends on their pH-dependent fusion with prostasomes, which are small vesicles secreted by the prostate. We found that prostasome fusion led to the transfer of progesterone receptors, cyclic adenosine diphosphoribose (cADPR) - synthesizing enzymes, ryanodine receptors (RyRs), and other Ca²⁺ signaling tools from prostasomes to the sperm neck. Progesterone-induced sperm motility relied on cADPR-mediated Ca²⁺ mobilization through RyR located on acidic Ca²⁺ stores, followed by Ca²⁺ entry through store-operated channels. Treatment of prostasome-fused sperm with a cADPR antagonist or fusion with prostasomes in which type 2 RyR was depleted resulted in low fertilization rates, reduced sperm motility, or both. Thus, we conclude that sperm motility depends on the acquisition of Ca²⁺ signaling tools from prostasomes.