Effect of NGF on the Motility and Acrosome Reaction of Golden Hamster Spermatozoa In Vitro

Abstract

Abstract. Motility and fertilizing ability are known to be two important physiological attributes of a mature sperm, yet the mechanism by which spermatozoa mature and become motile remains largely unknown. It has been shown that nerve growth factor (NGF) is a protein essential for the development, maintenance and survival of the peripheral and central nervous systems. However, the presence of high levels of NGF protein and mRNA do not correlate with the innervations by NGF sensitive fibers in tissues such as the testis, prostate and seminal vesicles. These observations have shifted the attention of research to the role of NGF outside of the nervous system. Here, we demonstrate that NGF and its receptors TrkA and p75 are widely expressed in the testis, accessory reproductive organ, and the epididymal sperms. We also show that NGF stimulates two important aspects of sperm functions, motility and the acrosome reaction, in a time-and dose-dependent manner. NGF activated the sperm cell acrosome reaction, while addition of inhibitors specific for MAPK kinase significantly blocked the sperm acrosome reaction. Taken together, our findings suggest that NGF plays an integral role in sperm motility and the acrosome reaction through, at least in part, the MAPK signalling pathway. Key words: Acrosome reaction, Golden hamster, Motility, Nerve growth factor (NGF), Sperm (J. Reprod. Dev. 56: [437][438][439][440][441][442][443] 2010) everal reports have established that the neurotropins, which include NGF, brain-derived neurotropic factor (BDNF), NT-3, NT-4 and NT-5, are essential factors concerning the development and maintenance of sympathetic and sensory peripheral neurons as well as central cholinergic neurons [1]. Effects of NGF have been shown to be mediated through specific membrane receptors of low-(p75) and high-(TrkA) affinity, the latter being responsible for most of its biological activities on neuronal tissues [1] and others [2][3][4].Each neurotrophin binds a specific Trk receptor tyrosine kinase [5], and its binding to Trk receptors results in receptor dimerization and kinase activation. Trk receptor phosphorylation promotes signaling cascades by creating docking sites for adaptor proteins that couple these receptors to pathways such as the Ras/extracellularsignal-regulated protein kinase (ERK) and mitogen-activated protein kinase (MAPK) pathways [6].Despite the central tropic effect of neurotrophins in the nervous system, high levels of NGF have been reported to exist outside the nervous system, particularly in the testis [7,8]. In addition, a substantial number of observations linking NGF to sperm development have been reported: high levels of NGF mRNA have been discovered in the lower mouse caput epididymis and corpus epididymis, suggesting a role for NGF in sperm maturation [7], testicular and germ cell atrophy following exposure to n-hexane leads to loss of NGF [9] and NGF has been found to be synthesized by spermatocytes and early spermatids [7]. NGF has already been implicated in sperm cell survival eith...

The potential roles of neurotrophins in male reproduction

“…In order to clarify the paracrine effects of NGF in spermatogenesis it is necessary to identify other NGF-regulated factors expressed by somatic cells in the testes (Mü ller et al 2006). Interestingly, recent studies have shown that NGF and TRKA are also present in the ejaculated sperm (Jin et al 2010, Li et al 2010a, 2010b and that in sperm samples from oligoasthenozoospermic men the levels of both NGF protein in the seminal plasma and TrkA mRNA in the spermatozoa are unusually low (Li et al 2010a(Li et al , 2010b. In bovine spermatozoa NGF immunoreactivity was localized to the heads and tails of the spermatozoa, whereas TRKA immunoreactivity was detected in the acrosomal cap, nucleus and tail regions, and treatment of the sperm with exogenous NGF for 2 h had significant effects on leptin secretion, cell viability and sperm apoptosis (Li et al 2010a(Li et al , 2010b.…”

“…In bovine spermatozoa NGF immunoreactivity was localized to the heads and tails of the spermatozoa, whereas TRKA immunoreactivity was detected in the acrosomal cap, nucleus and tail regions, and treatment of the sperm with exogenous NGF for 2 h had significant effects on leptin secretion, cell viability and sperm apoptosis (Li et al 2010a(Li et al , 2010b. NGF also stimulates sperm motility in a time-and dose-dependent manner in golden hamster spermatozoa in vitro and regulates the acrosome reaction via the MAPK signaling pathway (Jin et al 2010). Ejaculated mammalian spermatozoa are considered to be highly differentiated terminal cells in which no mRNA transcription or translation occurs.…”

Evidence for the involvement of NGF in human sperm motility

“…However, the expression of NT receptors in non-neuronal tissues and the effects strongly suggests that NTs have a broader range of actions than originally supposed. More and more data suggest a role in the regulation of non-nervous tissues of these molecules [2,3].…”

Selenium Increases Testicular Steroidogenesis and Growth Factors Expression in Streptozotocin-induced Diabetic Rats

“…In addition, Sertoli cells, spermatocytes, and early spermatids are known to synthesize NGF-β [25] , which is involved in sperm motility and acrosome reaction [26] . NFκB-mediated transcription of pro-inflammatory mediators [27] .…”