Ca ²⁺ Signaling Tools Acquired from Prostasomes Are Required for Progesterone-Induced Sperm Motility

Abstract

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.

A caged progesterone analog alters intracellular Ca2+ and flagellar bending in human sperm

“…These results indicate mPRa is a candidate for the progesterone receptor, which contributes a rapid Ca 2C influx in the flagellar mp. Just recently, it was reported that the prostasomes supply some membrane proteins to human sperm that modify their function (Park et al 2011). Although mouse sperm are usually obtained from the epididymis, human sperm are normally obtained from ejaculated semen.…”

Unraveling the sperm proteome and post-genomic pathways associated with sperm nuclear DNA fragmentation

“…Prostasomes interact directly with sperm, modulating its function [59][60][61] and protecting them against oxidative stress [62]. Human prostasomes can also be involved with sperm metabolism, because these vesicles express glycolytic enzymes [63].…”

Disruption of the principal, progesterone-activated sperm Ca 2+ channel in a CatSper2-deficient infertile patient

“…Therefore, mouse CatSper knockout models cannot be used. Another important unresolved issue is whether exposure to seminal plasma is an essential step for spermatozoa to acquire the ability to respond to progesterone (21) and whether the obvious lack of sensitivity of mouse CatSper to progesterone is because experiments were performed with epididymal mouse spermatozoa (18) that have never been exposed to seminal plasma. Here we apply the patch-clamp technique to spermatozoa isolated from a CatSper2-deficient infertile patient to provide genetic evidence that the CatSper channel constitutes a dominant Ca 2+ conductance of human spermatozoa that is potently activated by nanomolar concentrations of progesterone.…”