Functional characterization of a mouse testicular olfactory receptor and its role in chemosensing and in regulation of sperm motility

Although a subset of the olfactory receptor (OR) gene family is expressed in testis, neither their developmental profile nor their physiological functions have been fully characterized. Here, we show that MOR23 (a mouse OR expressed in the olfactory epithelium and testis) functions as a chemosensing receptor in mouse germ cells. In situ hybridization showed that MOR23 was expressed in round spermatids during stages VI-VIII of spermatogenesis. Lyral, a cognate ligand of MOR23, caused an increase in intracellular Ca²⁺ in a fraction of spermatogenic cells and spermatozoa. We also generated transgenic mice that express high levels of MOR23 in the testis and examined the response of their germ cells to lyral. The results provided evidence that lyral-induced Ca²⁺ increases were indeed mediated by MOR23. In a sperm accumulation assay, spermatozoa migrated towards an increasing gradient of lyral. Tracking and sperm flagellar analyses suggest that Ca²⁺ increases caused by MOR23 activation lead to modulation of flagellar configuration, resulting in chemotaxis. By contrast, a gradient of a cAMP analog or K8.6 solution, which elicit Ca²⁺ influx in spermatozoa, did not cause sperm accumulation, indicating that chemosensing and regulation of sperm motility was due to an OR-mediated local Ca²⁺ increase. The present studies indicate that mouse testicular ORs might play a role in chemoreception during sperm-egg communication and thereby regulate fertilization.