CatSper channel, sperm function and male fertility

Abstract

A number of physiological events, such as sperm hyperactivation, chemotaxis towards the egg, capacitation and acrosome reaction, are triggered by activation of sperm ion channels in response to a diverse range of chemical cues. Cation channel of sperm (CatSper), a sperm-specific ion channel, is unique in orchestrating the events for fertilization, and seems to be exclusively evolved for sperm function and male fertility. CatSper acts as a polymodal, chemosensory calcium channel and plays a vital role in the regulation of sperm hyperactivation. CatSper knockout models and application of patch clamp recordings have shown that it is indispensable for male fertility, and mutations and deletions in CatSper gene(s) may lead to infertility. In fact, mutations in CatSper1 and 2 have been identified in infertile individuals; however, CatSper3 and 4 have not been explored. Restricted localization and expression of CatSper in sperm offer an added advantage to developing gamete-based safe non-hormonal contraceptives. This review concisely covers identification, structure, function, and mechanism of action of CatSper channels. The functional importance of this complex ion channel in sperm motility and male fertility is highlighted for further research on male fertility, infertility, and contraception.

An Orchestrated Intron Retention Program in Meiosis Controls Timely Usage of Transcripts during Germ Cell Differentiation

“…Gene expression analyses revealed a remarkable and global reprogramming of the transcriptome across meiosis, with 12,726 genes (corresponding to nearly 60% of the expressed genes; data not shown) differentially expressed between spermatocytes and spermatids (Figure 1B). As expected, transcripts for the spermatid-specific nucleoproteins (i.e., protamines and transition proteins) (Dadoune, 2003) and the sperm-specific calcium channels (i.e., CatSper proteins) (Singh and Rajender, 2015) were strongly upregulated in spermatids (Figure S1A). By contrast, expression of the Sycp2 and Sycp3 genes, encoding synaptonemal proteins (Wang et al., 2005), and of Mlh3 and Spo11 , encoding homologous recombination proteins (Romanienko and Camerini-Otero, 2000, Santucci-Darmanin et al., 2002), were upregulated in spermatocytes (Figure S1A).…”

Regulation of Spermatogenic Cell T‐Type Ca2+ Currents by Zn2+: Implications in Male Reproductive Physiology

“…While the physiological relevance of macroscopic CatSper Ca 2+ currents is clear in regulating sperm hyperactivation, a particular form of motility which generates a more powerful swimming force required for successful fertilization; their potential contribution to the acrosome reaction requires further examination. Catsper knockout mice maintain intact spermatogenic cell I CaT (Ren et al, ), and the ability of their spermatozoa to undergo the acrosome reaction is similar to that of those from wild‐type mice (Xia and Ren, ; Singh and Rajender, ). Spermatozoa from CatSper1 null mice show a delayed ZP‐induced Ca 2+ rise that leads to acrosome reaction therefore, the potential contribution of Ca V 2.3 or Ca V 3.2 channels in this phenomenon should be further studied.…”

Sodium-Hydrogen-Exchanger expression in human sperm and its relationship with semen parameters

“…It is widely acknowledged that cAMP/protein kinase A (PKA)-dependent protein phosphorylation plays a crucial role in mediating the initiation and activation of sperm motility [4]. Moreover, the calcium signaling pathways are responsible for sperm motility [5]. The homeostasis between extra and intracellular calcium is required for development of both motility and hyperactivation of spermatozoa by activating the PKA or PKA-independent pathway.…”