Abstract
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.
Highlights
The G-protein-coupled olfactory receptors (ORs) make up a large multigene family that includes approximately 1000 members in mice (Zhang and Firestein, 2002)
The OR proteins appear to be expressed in late spermatids and on the tail midpiece of mature spermatozoa, implying that testicular ORs are involved in sperm maturation, migration or fertilization (Vanderhaeghen et al, 1993; Walensky et al, 1995)
Reverse-transcriptase polymerase chain reaction (PCR) (RT-PCR) analysis showed that MOR23 is expressed in both the olfactory epithelium and the testis, but not in the vomeronasal organ, ovary, brain or kidney (Fig. 1A)
Summary
The G-protein-coupled olfactory receptors (ORs) make up a large multigene family that includes approximately 1000 members in mice (Zhang and Firestein, 2002). Some of the components in the olfactory pathways, such as Gαolf, adenylyl cyclase III and CNG channels, are expressed in testis and sperm (Defer et al, 1998; Gautier-Courteille et al, 1998; Weyand et al, 1994; Wiesner et al, 1998), suggesting that testicular ORs can recruit the same cAMP-Ca2+ signaling cascade as in the olfactory epithelium This concept is supported by the finding that β-arrestin, which might mediate the desensitization of ORs, is localized with OR proteins in the mid-piece of rat sperm (Dawson et al, 1993; Walensky et al., 1995). Resact, a chemoattractant peptide from the sea urchin (Ward et al, 1985), binds to a membrane receptor on sperm and increases cGMP levels, followed by a transient influx of Ca2+
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
