Abstract

In addition to odorant receptor (OR) expression in sensory neurons of the olfactory epithelium, some OR proteins are also found in ectopic tissues, e.g. in testis. In mammals, such testicular ORs have been attributed a potential function as molecular switches of unique sperm swimming behaviors. Using a combination of recombinant receptor expression in HEK293 cells, single cell calcium imaging, sperm accumulation assays, flagellar beating and video motion analysis, we recently identified and functionally characterized a human testicular OR, OR1D2 (a.k.a. hOR17-4), that specifically responds to a subset of structurally similar floral odors (e.g. bourgeonal) and triggers chemotactic and chemokinetic sperm responses in vitro. In addition, we here report functional description of two novel putative sperm ORs. With respect to their individual physiological roles in vivo, however, several crucial questions remain. First, are these ORs actually functional in human sperm? Second, do they trigger common or distinct signaling pathways, evoking similar or OR-specific behavioral responses? Third, is the popular “one cell - one receptor” rule that applies to olfactory neurons also applicable to sperm? Comparative analysis of receptor-specific activation profiles reveals non-overlapping molecular receptive fields as well as distinct susceptibility to antagonistic odors. Activation of individual ORs in human sperm mediates distinct behavioral response patterns. Our findings thus support the notion that OR-dependent signaling pathways could play a substantial role in various pre-fusion aspects of sperm physiology.

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