Are the Olfactory Receptors Present at the Sperm Membrane Involved in Reproduction?

Olfactory receptors (ORs), key components in ensuring the detection of myriad odorants, are expressed not only on the surface of olfactory neurons but also in many other tissues. In the case of ORs expressed at the sperm membrane, in vitro experiments with human and mouse spermatozoids have shown that they move toward the regions with the highest concentration of bourgeonal and lyral, respectively. However, to date, no in vivo experiment has shown any biological function of these ORs. To demonstrate a possible role in vivo of ORs in sperm chemotaxis, we overloaded the vaginal space of female mice from the prolific Swiss CD1 strain with lyral to induce competition with the supposed natural ligand and to prevent its detection. As shown, the mice that received lyral had much fewer newborns than the control mice treated with PBS, showing that lyral has a strong negative impact on procreation. This indicates that the ORs at the sperm surface are biologically active and make an important contribution to reproduction. Control experiments performed with hexanal, which does not alter sperm movement in vitro, indicate that the inhibition of reproduction observed was specific to lyral. In addition, we show that males are attracted to the smell of lyral, which acts as a pheromone, and prefer to copulate with mice marked on their back with lyral rather than with those that have not been marked. These results suggest an explanation for some cases of human infertility, which could result from an absence of recognition between the natural ligand and the ORs, either due to a mutation or a lack of expression from one of the two partners, allowing for the development of a diagnostic tests. These results might also lead to the development of a novel contraception strategy based on the use of vaginal tablets delivering an odorant or a drug that competes with the natural ligand.