Chloride channels are involved in sperm motility and are downregulated in spermatozoa from patients with asthenozoospermia

Abstract

Human spermatozoa encounter an osmotic decrease from 330 to 290 mOsm l−1 when passing through the female reproductive tract. We aimed to evaluate the role of chloride channels in volume regulation and sperm motility from patients with asthenozoospermia. Spermatozoa were purified using Percoll density gradients. Sperm volume was measured as the forward scatter signal using flow cytometry. Sperm motility was analyzed using computer-aided sperm analysis (CASA). When transferred from an isotonic solution (330 mOsm l−1) to a hypotonic solution (290 mOsm l−1), cell volume was not changed in spermatozoa from normozoospermic men; but increased in those from asthenozoospermic samples. The addition of the chloride channel blockers, 4,4′-diisothiocyanatostilbene-2,2′- isulfonic acid (DIDS) or 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) to the hypotonic solution caused the normal spermatozoa to swell but did not increase the volume of those from the asthenozoospermic semen. DIDS and NPPB decreased sperm motility in both sets of semen samples. The inhibitory effect of NPPB on normal sperm motility was much stronger than on spermatozoa from the asthenozoospermic samples. Both sperm types expressed ClC-3 chloride channels, but the expression levels in the asthenozoospermic samples were much lower, especially in the neck and mid-piece areas. Spermatozoa from men with asthenozoospermia demonstrated lower volume regulating capacity, mobility, and ClC-3 expression levels (especially in the neck) than did normal spermatozoa. Thus, chloride channels play important roles in the regulation of sperm volume and motility and are downregulated in cases of asthenozoospermia.

Forensic Relationship between ATP6 Gene and Sperm Motility in a Saudi Population

“…In spite of this approved identification, published evidence for classifying the samples into normospermic, teratospermic, oligospermic and asthenospermic as listed in WHO (2010) criteria was presented herein. Ji et al (2017) and Liu et al (2017) identified the different infertility cases according to sperm count and motility. Asthenospermia was identified by reduction in sperm motility lower than 40% motile sperms.…”

Molecular Changes Induced by Oxidative Stress that Impair Human Sperm Motility

“…The disruption of sperm membrane integrity alters the diffusion of ions across the membrane and dysregulates the function of ion pumps and channels, especially as those ion channels that are regulated by PUFAs (reviewed in [90]). Although there is currently limited direct evidence linking sperm membrane integrity and ion channel function, the peroxidation of lipids and the downregulation of some ion channels in low-motility spermatozoa has been documented [83,[91][92][93][94]. In this context, Baker et al [22] reported two sperm ion channels, voltage-dependent anion-selective channel protein 2 (VDAC2) and sodium/potassium-transporting ATPase subunit alpha-4 (ATP1A4) that are susceptible to the formation of potentially deleterious adducts with 4HNE.…”

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

“…In view of the complexity of the regulatory pathways in sperm motility, it appears that any abnormalities of these pathways could contribute to impaired sperm motility. For example, mutation of a sperm-specific subunit of PKA does not affect the process of spermatogenesis, but impairs the capability of forward motility in mature sperm [6]; aberrated expression of the ion channel, such as with the voltage-dependent anion channel and chloride channels, could result in poor sperm motility and consequently asthenozoospermia [7,8].…”