Characterization of the kisspeptin system in human spermatozoa

Abstract

Summary Kisspeptin, the product of the KISS1 gene, plays an essential role in the regulation of spermatogenesis acting primarily at the hypothalamic level of the gonadotropic axis. However, the presence of kisspeptin and its canonical receptor, KISS1R, in spermatozoa has not been explored nor the direct effects of kisspeptin on sperm function have been studied so far. In the present study, we analysed the expression of kisspeptin and its receptor in sperm cells by western blot and immunocytochemistry assays and evaluated the effects of exposure to kisspeptin on sperm intracellular Ca2+ concentration, [Ca2+]i, sperm motility, sperm hyperactivation and the acrosome reaction. Changes in [Ca2+]i were monitored using Fura‐2, sperm kinematic parameters were measured using computer‐assisted sperm analysis (CASA), and the acrosome reaction was measured using fluorescein isothiocyanate‐coupled Pisum sativum agglutinin lectin (FITC–PSA method). We found that kisspeptin and its receptor are present in sperm cells, where both are mainly localized in the sperm head, around the neck and in the flagellum midpiece. Exposure to kisspeptin caused a slow, progressive increase in [Ca2+]i, which reached a plateau about 3–6 min after kisspeptin exposure. In addition, kisspeptin modulated sperm progressive motility causing a biphasic (stimulatory and inhibitory) response and also induced transient sperm hyperactivation. The effects of kisspeptin on sperm motility and hyperactivation were inhibited by the antagonist of KISS1R, peptide 234. Kisspeptin did not induce the acrosome reaction in human spermatozoa. These data show for the first time that kisspeptin and its receptor are present in human spermatozoa and modulate key parameters of sperm function. This may represent an additional mechanism for their crucial function in the control of male fertility.

Kisspeptin modulates fertilization capacity of mouse spermatozoa

“…Further experiments are needed to clarify whether kisspeptin acts on germ cells in testis tissue. Mature mouse sperm from cauda epididymis retain KISS1R at the acrosomal region, consistent with previous results in human sperm (Pinto et al 2012). The current results reveal that kisspeptin 10 treatment induces concentration-dependent [Ca 2C ] i increases.…”

“…Kiss1 and Kiss1r gene expression has been reported in human and rodent testes (Ohtaki et al 2001, Terao et al 2004, Zhao et al 2010; however, protein expression and function were incompletely understood. Recently, kisspeptin and KISS1R were detected in human spermatozoa and found to affect motility (Pinto et al 2012). A previous study showed that kisspeptin was present in the oviduct, suggesting that kisspeptin may participate in capacitation, acrosome reaction, and/or fertilization.…”

Rola sygnalizacji kisspeptyny w osi podwzgórze–przysadka–nadnercza — aktualna perspektywa

“…It has been evidenced by detection of kisspeptin and its receptor in human sperm, which could be activated by kisspeptin treatment while sperm activity was blocked by kisspeptin antagonists [177]. Similarly, Kiss1 and Kiss1r have been detected in the testes of mice and have been suggested to regulate sperm function, although kisspeptins failed to release testosterone form seminiferous tubule explants [178,179].…”

Endocannabinoids and Kisspeptins: Two Modulators in Fight for the Regulation of GnRH Activity

“…To date, in species with external fertilization ECBs control the number of motile spermatozoa keeping sperm motility quiescent until their release in aquatic environment (Cobellis et al, 2006). In vitro, kisspeptin stimulates an irregular flagellar beating that is typical of a hyperactivation state, a condition critical for fertilization (Pinto et al, 2012). Then, it is intriguing to note that CB1, but not kisspeptin, controls the zona pellucida induced acrosome reaction (Wang et al, 2006) and GnRH increases spermzona pellucida binding in humans (Morales et al, 2002b).…”

“…Mammalian spermatozoa acquire the ability to swim during their transit from the testis to the oviduct under the control of several external and intracellular factors. In vertebrates, spermatozoa possess a complete ECS and, at least in humans, evidence of kisspeptin system activity has been provided (Pinto et al, 2012;Wang et al, 2006). ECBs, via CB1, operate into the epididymis to regulate sperm motility acquisition and to prevent premature acrosome reaction (Cobellis et al, 2010;Ricci et al, 2007;Wang et al, 2006).…”