Identification of a Testicular Odorant Receptor Mediating Human Sperm Chemotaxis

TLDR

Although it has been known for some time that olfactory receptors (ORs) reside in spermatozoa, the function of these ORs is unknown. With ratiofluorometric imaging, Ca²⁺ signals were induced by a small subset of chemical stimuli, defining the molecular receptive fields of the recombinantly expressed receptor in HEK 293 cells and the native receptor in human spermatozoa. We identified, cloned, and functionally expressed the previously undescribed human testicular odorant receptor hOR17‑4, found that bourgeonal is a potent agonist and chemoattractant while undecanal acts as an antagonist, and concluded that hOR17‑4 mediates human sperm chemotaxis and may be essential for fertilization.

Abstract

Although it has been known for some time that olfactory receptors (ORs) reside in spermatozoa, the function of these ORs is unknown. Here, we identified, cloned, and functionally expressed a previously undescribed human testicular OR, hOR17-4. With the use of ratiofluorometric imaging, Ca2+ signals were induced by a small subset of applied chemical stimuli, establishing the molecular receptive fields for the recombinantly expressed receptor in human embryonic kidney (HEK) 293 cells and the native receptor in human spermatozoa. Bourgeonal was a powerful agonist for both recombinant and native receptor types, as well as a strong chemoattractant in subsequent behavioral bioassays. In contrast, undecanal was a potent OR antagonist to bourgeonal and related compounds. Taken together, these results indicate that hOR17-4 functions in human sperm chemotaxis and may be a critical component of the fertilization process.