Chemosensory Ca2+ Dynamics Correlate with Diverse Behavioral Phenotypes in Human Sperm

In the female reproductive tract, mammalian sperm undergo a regulated sequence of prefusion changes that “prime” sperm for fertilization. Among the least understood of these complex processes are the molecular mechanisms that underlie sperm guidance by environmental chemical cues. A “hard-wired” Ca2+ signaling strategy that orchestrates specific motility patterns according to given functional requirements is an emerging concept for regulation of sperm swimming behavior. The molecular players involved, the spatiotemporal characteristics of such motility-associated Ca2+ dynamics, and the relation between a distinct Ca2+ signaling pattern and a behavioral sperm phenotype, however, remain largely unclear. Here, we report the functional characterization of two human sperm chemoreceptors. Using complementary molecular, physiological, and behavioral approaches, we comparatively describe sperm Ca2+ responses to specific agonists of these novel receptors and bourgeonal, a known sperm chemoattractant. We further show that individual receptor activation induces specific Ca2+ signaling patterns with unique spatiotemporal dynamics. These distinct Ca2+ dynamics are correlated to a set of stimulus-specific stereotyped behavioral responses that could play vital roles during various stages of prefusion sperm-egg chemical communication.