Autocrine regulation of human sperm motility by tachykinins

Abstract

BackgroundWe examined the presence and function of tachykinins and the tachykinin-degrading enzymes neprilysin (NEP) and neprilysin-2 (NEP2) in human spermatozoa.MethodsFreshly ejaculated semen was collected from forty-eight normozoospermic human donors. We analyzed the expression of substance P, neurokinin A, neurokinin B, hemokinin-1, NEP and NEP2 in sperm cells by reverse-transcriptase polymerase chain reaction (RT-PCR), western blot and immunocytochemistry assays and evaluated the effects of the neprilysin and neprilysin-2 inhibitor phosphoramidon on sperm motility in the absence and presence of tachykinin receptor-selective antagonists. Sperm motility was measured using WHO procedures or computer-assisted sperm analysis (CASA).ResultsThe mRNAs of the genes that encode substance P/neurokinin A (TAC1), neurokinin B (TAC3), hemokinin-1 (TAC4), neprilysin (MME) and neprilysin-2 (MMEL1) were expressed in human sperm. Immunocytochemistry studies revealed that tachykinin and neprilysin proteins were present in spermatozoa and show specific and differential distributions. Phosphoramidon increased sperm progressive motility and its effects were reduced in the presence of the tachykinin receptor antagonists SR140333 (NK1 receptor-selective) and SR48968 (NK2 receptor-selective) but unmodified in the presence of SR142801 (NK3 receptor-selective).ConclusionThese data show that tachykinins are present in human spermatozoa and participate in the regulation of sperm motility. Tachykinin activity is regulated, at least in part, by neprilysins.

Autocrine regulation of human sperm motility by the met-enkephalin opioid peptide

“…This hypothesis is consistent with previous work where variable levels of enkephalins, as well as other opioid peptides, have been reported in the female reproductive tracts of cows (40), and both opioid receptors and enkephalin degrading enzymes have been shown to be involved in sperm motility in a distinct manner (37). Moreover, enkephalins, together with other biopeptides such as tachykinins (24,39), could operate as molecular signals between spermatozoa and their environment in order for sperm cells to become fertilization competent. Elucidating the dynamic, functional, and morphological changes that occur in sperm cells will be important to understand the fertilization process, and it will be interesting to determine whether deregulation of these systems may contribute to male factor infertility.…”

“…On the other hand, the leuhistin and thiorphan inhibitors improved sperm motility at 1 hour, but this effect was not reversed by naloxone. This suggests that enkephalin-degrading enzymes can enhance sperm motility by mechanisms, which do not involve opioid receptors, since both of these inhibitory enzymes can participate in the degradation of other peptides, such as bradykinins or tachykinins, which are present in sperm cells (24,39).…”

Inhibitors of endopeptidase and angiotensin-converting enzyme lead to an amplification of the morphological changes and an upregulation of the substance P system in a muscle overuse model

“…SP is known to have trophic and healing effects [19,38], including in the initial stages of Achilles tendon healing in the rat [22]. Rats with high residual SP levels after capsaicin-induced neuropathy showed more improvements than those with low levels in the healing of the rat Achilles tendon [39].…”

GPCR Heterodimerization in the Reproductive System: Functional Regulation and Implication for Biodiversity

“…In the ascidian, Ciona intestinalis , authentic TK, and its cognate receptor, Ci-TK-I and Ci-TK-R were identified (49, 50). Recently, there are accumulating reports on reproductive roles of TKs as well as the expression of TKs and TK receptors in genital organs of mammals (46, 48, 49, 51–54). In C. intestinalis , Ci-TK-I enhances oocyte growth from the vitellogenic stage to the post-vitellogenic stage via upregulation of gene expression and enzymatic activity of several proteases such as cathepsin D, carboxypeptidase B1, and chymotrypsin (55–57).…”