A role for tachykinins in the regulation of human sperm motility

BACKGROUND: Tachykinins and tachykinin receptors are widely distributed in the male reproductive tract and appear to be involved in reproduction. However, the function and expression of tachykinins and their receptors in human spermatozoa remain poorly studied. We analysed the effects of tachykinins on sperm motility and characterized the population of tachykinin receptors in human spermatozoa. METHODS AND RESULTS: Motility analysis was performed following World Health Organization guidelines and we found that substance P (SP), human hemokinin-1 (hHK-1), neurokinin A (NKA) and neurokinin B (NKB) produced concentration-dependent increases in sperm progressive motility. The effects of tachykinins were antagonized by the NK 1 receptor-selective antagonist SR 140333, the NK 2 receptor-selective antagonist, SR 48968 and, to a lesser extent, also by the NK 3 receptor-selective antagonist SR 142801. Immunocytochemistry studies showed expression of the NK 1 , NK 2 and NK 3 tachykinin receptor proteins in spermatozoa with different major sites of localization for each receptor. Western blot analysis confirmed the presence of tachykinin receptors in sperm cell homogenates. RT-PCR demonstrated expression of the genes that encode SP/NKA (TACT), NKB (TAC3) and hHK-1 (TAC4) but not the genes TACR1, TACR2 and TACR3 encoding NK 1 , NK 2 and NK 3 receptors, respectively. CONCLUSIONS: These results show for the first time that the NK 1 , NK 2 and NK 3 tachykinin receptor proteins are present in human spermatozoa. Our findings suggest that tachykinins, probably acting through these three tachykinin receptors, play a role in the regulation of human sperm motility.