International Journal of Molecular Sciences

Editorial

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4 pages, 548 KiB

Open AccessEditorial

Ion Channels of Spermatozoa: Structure, Function, and Regulation Mechanisms

by Elisabeth Pinart

Int. J. Mol. Sci. 2022, 23(11), 5880; https://doi.org/10.3390/ijms23115880 - 24 May 2022

Cited by 1 | Viewed by 1380

Abstract

Ion transport is essential for sperm physiology, being involved in sperm-cell differentiation and maturation, motility activation, chemotaxis towards the oocyte, and fertilization, as well as in sperm adaptation to the surrounding medium [...] Full article

(This article belongs to the Special Issue Ion Channels of Spermatozoa: Structure, Function and Regulation Mechanisms)

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Research

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12 pages, 2859 KiB

Open AccessArticle

Kcnj16 (Kir5.1) Gene Ablation Causes Subfertility and Increases the Prevalence of Morphologically Abnormal Spermatozoa

by Giulia Poli, Sonia Hasan, Silvia Belia, Marta Cenciarini, Stephen J. Tucker, Paola Imbrici, Safa Shehab, Mauro Pessia, Stefano Brancorsini and Maria Cristina D'Adamo

Int. J. Mol. Sci. 2021, 22(11), 5972; https://doi.org/10.3390/ijms22115972 - 1 Jun 2021

Cited by 5 | Viewed by 3104

Abstract

The ability of spermatozoa to swim towards an oocyte and fertilize it depends on precise K⁺ permeability changes. Kir5.1 is an inwardly-rectifying potassium (Kir) channel with high sensitivity to intracellular H⁺ (pHi) and extracellular K⁺ concentration [K⁺]_o [...] Read more.

The ability of spermatozoa to swim towards an oocyte and fertilize it depends on precise K⁺ permeability changes. Kir5.1 is an inwardly-rectifying potassium (Kir) channel with high sensitivity to intracellular H⁺ (pHi) and extracellular K⁺ concentration [K⁺]_o, and hence provides a link between pHi and [K⁺]_o changes and membrane potential. The intrinsic pHi sensitivity of Kir5.1 suggests a possible role for this channel in the pHi-dependent processes that take place during fertilization. However, despite the localization of Kir5.1 in murine spermatozoa, and its increased expression with age and sexual maturity, the role of the channel in sperm morphology, maturity, motility, and fertility is unknown. Here, we confirmed the presence of Kir5.1 in spermatozoa and showed strong expression of Kir4.1 channels in smooth muscle and epithelial cells lining the epididymal ducts. In contrast, Kir4.2 expression was not detected in testes. To examine the possible role of Kir5.1 in sperm physiology, we bred mice with a deletion of the Kcnj16 (Kir5.1) gene and observed that 20% of Kir5.1 knock-out male mice were infertile. Furthermore, 50% of knock-out mice older than 3 months were unable to breed. By contrast, 100% of wild-type (WT) mice were fertile. The genetic inactivation of Kcnj16 also resulted in smaller testes and a greater percentage of sperm with folded flagellum compared to WT littermates. Nevertheless, the abnormal sperm from mutant animals displayed increased progressive motility. Thus, ablation of the Kcnj16 gene identifies Kir5.1 channel as an important element contributing to testis development, sperm flagellar morphology, motility, and fertility. These findings are potentially relevant to the understanding of the complex pHi- and [K⁺]_o-dependent interplay between different sperm ion channels, and provide insight into their role in fertilization and infertility. Full article

(This article belongs to the Special Issue Ion Channels of Spermatozoa: Structure, Function and Regulation Mechanisms)

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17 pages, 1872 KiB

Open AccessArticle

Inhibition of Potassium Channels Affects the Ability of Pig Spermatozoa to Elicit Capacitation and Trigger the Acrosome Exocytosis Induced by Progesterone

by Federico Noto, Sandra Recuero, Julián Valencia, Beatrice Saporito, Domenico Robbe, Sergi Bonet, Augusto Carluccio and Marc Yeste

Int. J. Mol. Sci. 2021, 22(4), 1992; https://doi.org/10.3390/ijms22041992 - 17 Feb 2021

Cited by 8 | Viewed by 2726

Abstract

During capacitation, sperm undergo a myriad of changes, including remodeling of plasma membrane, modification of sperm motility and kinematic parameters, membrane hyperpolarization, increase in intracellular calcium levels, and tyrosine phosphorylation of certain sperm proteins. While potassium channels have been reported to be crucial [...] Read more.

During capacitation, sperm undergo a myriad of changes, including remodeling of plasma membrane, modification of sperm motility and kinematic parameters, membrane hyperpolarization, increase in intracellular calcium levels, and tyrosine phosphorylation of certain sperm proteins. While potassium channels have been reported to be crucial for capacitation of mouse and human sperm, their role in pigs has not been investigated. With this purpose, sperm samples from 15 boars were incubated in capacitation medium for 300 min with quinine, a general blocker of potassium channels (including voltage-gated potassium channels, calcium-activated potassium channels, and tandem pore domain potassium channels), and paxilline (PAX), a specific inhibitor of calcium-activated potassium channels. In all samples, acrosome exocytosis was induced after 240 min of incubation with progesterone. Plasma membrane and acrosome integrity, membrane lipid disorder, intracellular calcium levels, mitochondrial membrane potential, and total and progressive sperm motility were evaluated after 0, 120, and 240 min of incubation, and after 5, 30, and 60 min of progesterone addition. Although blocking potassium channels with quinine and PAX prevented sperm to elicit in vitro capacitation by impairing motility and mitochondrial function, as well as reducing intracellular calcium levels, the extent of that inhibition was larger with quinine than with PAX. Therefore, while our data support that calcium-activated potassium channels are essential for sperm capacitation in pigs, they also suggest that other potassium channels, such as the voltage-gated, tandem pore domain, and mitochondrial ATP-regulated ones, are involved in that process. Thus, further research is needed to elucidate the specific functions of these channels and the mechanisms underlying its regulation during sperm capacitation. Full article

(This article belongs to the Special Issue Ion Channels of Spermatozoa: Structure, Function and Regulation Mechanisms)

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17 pages, 4761 KiB

Open AccessArticle

HVCN1 but Not Potassium Channels Are Related to Mammalian Sperm Cryotolerance

by Ariadna Delgado-Bermúdez, Yentel Mateo-Otero, Marc Llavanera, Sergi Bonet, Marc Yeste and Elisabeth Pinart

Int. J. Mol. Sci. 2021, 22(4), 1646; https://doi.org/10.3390/ijms22041646 - 6 Feb 2021

Cited by 2 | Viewed by 1889

Abstract

Little data exist about the physiological role of ion channels during the freeze–thaw process in mammalian sperm. Herein, we determined the relevance of potassium channels, including SLO1, and of voltage-gated proton channels (HVCN1) during mammalian sperm cryopreservation, using the pig as a model [...] Read more.

Little data exist about the physiological role of ion channels during the freeze–thaw process in mammalian sperm. Herein, we determined the relevance of potassium channels, including SLO1, and of voltage-gated proton channels (HVCN1) during mammalian sperm cryopreservation, using the pig as a model and through the addition of specific blockers (TEA: tetraethyl ammonium chloride, PAX: paxilline or 2-GBI: 2-guanidino benzimidazole) to the cryoprotective media at either 15 °C or 5 °C. Sperm quality of the control and blocked samples was performed at 30- and 240-min post-thaw, by assessing sperm motility and kinematics, plasma and acrosome membrane integrity, membrane lipid disorder, intracellular calcium levels, mitochondrial membrane potential, and intracellular O₂⁻⁻ and H₂O₂ levels. General blockade of K⁺ channels by TEA and specific blockade of SLO1 channels by PAX did not result in alterations in sperm quality after thawing as compared to control samples. In contrast, HVCN1-blocking with 2-GBI led to a significant decrease in post-thaw sperm quality as compared to the control, despite intracellular O₂⁻⁻ and H₂O₂ levels in 2-GBI blocked samples being lower than in the control and in TEA- and PAX-blocked samples. We can thus conclude that HVCN1 channels are related to mammalian sperm cryotolerance and have an essential role during cryopreservation. In contrast, potassium channels do not seem to play such an instrumental role. Full article

(This article belongs to the Special Issue Ion Channels of Spermatozoa: Structure, Function and Regulation Mechanisms)

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12 pages, 6360 KiB

Open AccessArticle

Na⁺/H⁺ Exchangers Involve in Regulating the pH-Sensitive Ion Channels in Mouse Sperm

by Hang Kang, Min Liu, Wei Zhang, Rong-Zu Huang, Na Zhao, Chen Chen and Xu-Hui Zeng

Int. J. Mol. Sci. 2021, 22(4), 1612; https://doi.org/10.3390/ijms22041612 - 5 Feb 2021

Cited by 12 | Viewed by 1881

Abstract

Sperm-specific K⁺ ion channel (KSper) and Ca²⁺ ion channel (CatSper), whose elimination causes male infertility in mice, determine the membrane potential and Ca²⁺ influx, respectively. KSper and CatSper can be activated by cytosolic alkalization, which occurs during sperm going through [...] Read more.

Sperm-specific K⁺ ion channel (KSper) and Ca²⁺ ion channel (CatSper), whose elimination causes male infertility in mice, determine the membrane potential and Ca²⁺ influx, respectively. KSper and CatSper can be activated by cytosolic alkalization, which occurs during sperm going through the alkaline environment of the female reproductive tract. However, which intracellular pH (pH_i) regulator functionally couples to the activation of KSper/CatSper remains obscure. Although Na⁺/H⁺ exchangers (NHEs) have been implicated to mediate pH_i in sperm, there is a lack of direct evidence confirming the functional coupling between NHEs and KSper/CatSper. Here, 5-(N,N-dimethyl)-amiloride (DMA), an NHEs inhibitor that firstly proved not to affect KSper/CatSper directly, was chosen to examine NHEs function on KSper/CatSper in mouse sperm. The results of patch clamping recordings showed that, when extracellular pH was at the physiological level of 7.4, DMA application caused KSper inhibition and the depolarization of membrane potential when pipette solutions were not pH-buffered. In contrast, these effects were minimized when pipette solutions were pH-buffered, indicating that they solely resulted from pH_i acidification caused by NHEs inhibition. Similarly, DMA treatment reduced CatSper current and intracellular Ca²⁺, effects also dependent on the buffer capacity of pH in pipette solutions. The impairment of sperm motility was also observed after DMA incubation. These results manifested that NHEs activity is coupled to the activation of KSper/CatSper under physiological conditions. Full article

(This article belongs to the Special Issue Ion Channels of Spermatozoa: Structure, Function and Regulation Mechanisms)

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15 pages, 2610 KiB

Open AccessArticle

Polyamines Influence Mouse Sperm Channels Activity

by Lorena Rodríguez-Páez, Charmina Aguirre-Alvarado, Norma Oviedo, Verónica Alcántara-Farfán, Edgar E. Lara-Ramírez, Guadalupe Elizabeth Jimenez-Gutierrez and Joaquín Cordero-Martínez

Int. J. Mol. Sci. 2021, 22(1), 441; https://doi.org/10.3390/ijms22010441 - 4 Jan 2021

Cited by 6 | Viewed by 3208

Abstract

Polyamines are ubiquitous polycationic compounds that are highly charged at physiological pH. While passing through the epididymis, sperm lose their capacity to synthesize the polyamines and, upon ejaculation, again come into contact with the polyamines contained in the seminal fluid, unleashing physiological events [...] Read more.

Polyamines are ubiquitous polycationic compounds that are highly charged at physiological pH. While passing through the epididymis, sperm lose their capacity to synthesize the polyamines and, upon ejaculation, again come into contact with the polyamines contained in the seminal fluid, unleashing physiological events that improve sperm motility and capacitation. In the present work, we hypothesize about the influence of polyamines, namely, spermine, spermidine, and putrescine, on the activity of sperm channels, evaluating the intracellular concentrations of chloride [Cl⁻]i, calcium [Ca²⁺]i, sodium [Na⁺]i, potassium [K⁺]i, the membrane V_m, and pHi. The aim of this is to identify the possible regulatory mechanisms mediated by the polyamines on sperm-specific channels under capacitation and non-capacitation conditions. The results showed that the presence of polyamines did not directly influence the activity of calcium and chloride channels. However, the results suggested an interaction of polyamines with sodium and potassium channels, which may contribute to the membrane V_m during capacitation. In addition, alkalization of the pHi revealed the possible activation of sperm-specific Na⁺/H⁺ exchangers (NHEs) by the increased levels of cyclic AMP (cAMP), which were produced by soluble adenylate cyclase (sAC) and interact with the polyamines, evidence that is supported by in silico analysis. Full article

(This article belongs to the Special Issue Ion Channels of Spermatozoa: Structure, Function and Regulation Mechanisms)

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22 pages, 5420 KiB

Open AccessArticle

HVCN1 Channels Are Relevant for the Maintenance of Sperm Motility During In Vitro Capacitation of Pig Spermatozoa

by Marc Yeste, Marc Llavanera, Yentel Mateo-Otero, Jaime Catalán, Sergi Bonet and Elisabeth Pinart

Int. J. Mol. Sci. 2020, 21(9), 3255; https://doi.org/10.3390/ijms21093255 - 4 May 2020

Cited by 17 | Viewed by 3066

Abstract

The objective of the present study was to determine the physiological role of voltage-gated hydrogen channels 1 (HVCN1 channels) during in vitro capacitation of pig spermatozoa. Sperm samples from 20 boars were incubated in capacitating medium for 300 minutes (min) in the presence [...] Read more.

The objective of the present study was to determine the physiological role of voltage-gated hydrogen channels 1 (HVCN1 channels) during in vitro capacitation of pig spermatozoa. Sperm samples from 20 boars were incubated in capacitating medium for 300 minutes (min) in the presence of 2-guanidino benzimidazole (2-GBI), a specific HVCN1-channel blocker, added either at 0 min or after 240 min of incubation. Control samples were incubated in capacitating medium without the inhibitor. In all samples, acrosomal exocytosis was triggered with progesterone after 240 min of incubation. Sperm viability, sperm motility and kinematics, acrosomal exocytosis, membrane lipid disorder, intracellular calcium levels and mitochondrial membrane potential were evaluated after 0, 60, 120, 180, 240, 250, 270 and 300 min of incubation. While HVCN1-blockage resulted in altered sperm viability, sperm motility and kinematics and reduced mitochondrial membrane potential as compared to control samples, at any blocker concentration and incubation time, it had a non-significant effect on intracellular Ca²⁺ levels determined through Fluo3-staining. The effects on acrosomal exocytosis were only significant in blocked samples at 0 min, and were associated with increased membrane lipid disorder and Ca²⁺ levels of the sperm head determined through Rhod5-staining. In conclusion, HVCN1 channels play a crucial role in the modulation of sperm motility and kinematics, and in Ca²⁺ entrance to the sperm head. Full article

(This article belongs to the Special Issue Ion Channels of Spermatozoa: Structure, Function and Regulation Mechanisms)

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Review

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20 pages, 2363 KiB

Open AccessReview

Role and Modulation of TRPV1 in Mammalian Spermatozoa: An Updated Review

by Marina Ramal-Sanchez, Nicola Bernabò, Luca Valbonetti, Costanza Cimini, Angela Taraschi, Giulia Capacchietti, Juliana Machado-Simoes and Barbara Barboni

Int. J. Mol. Sci. 2021, 22(9), 4306; https://doi.org/10.3390/ijms22094306 - 21 Apr 2021

Cited by 14 | Viewed by 3255

Abstract

Based on the abundance of scientific publications, the polymodal sensor TRPV1 is known as one of the most studied proteins within the TRP channel family. This receptor has been found in numerous cell types from different species as well as in spermatozoa. The [...] Read more.

Based on the abundance of scientific publications, the polymodal sensor TRPV1 is known as one of the most studied proteins within the TRP channel family. This receptor has been found in numerous cell types from different species as well as in spermatozoa. The present review is focused on analyzing the role played by this important channel in the post-ejaculatory life of spermatozoa, where it has been described to be involved in events such as capacitation, acrosome reaction, calcium trafficking, sperm migration, and fertilization. By performing an exhaustive bibliographic search, this review gathers, for the first time, all the modulators of the TRPV1 function that, to our knowledge, were described to date in different species and cell types. Moreover, all those modulators with a relationship with the reproductive process, either found in the female tract, seminal plasma, or spermatozoa, are presented here. Since the sperm migration through the female reproductive tract is one of the most intriguing and less understood events of the fertilization process, in the present work, chemotaxis, thermotaxis, and rheotaxis guiding mechanisms and their relationship with TRPV1 receptor are deeply analyzed, hypothesizing its (in)direct participation during the sperm migration. Last, TRPV1 is presented as a pharmacological target, with a special focus on humans and some pathologies in mammals strictly related to the male reproductive system. Full article

(This article belongs to the Special Issue Ion Channels of Spermatozoa: Structure, Function and Regulation Mechanisms)

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16 pages, 879 KiB

Open AccessReview

Role of the Glycosylphosphatidylinositol-Anchored Protein TEX101 and Its Related Molecules in Spermatogenesis

by Hiroshi Yoshitake and Yoshihiko Araki

Int. J. Mol. Sci. 2020, 21(18), 6628; https://doi.org/10.3390/ijms21186628 - 10 Sep 2020

Cited by 9 | Viewed by 4735

Abstract

Glycosylphosphatidylinositol (GPI)-anchored proteins (APs) on the plasma membrane are involved in several cellular processes, including sperm functions. Thus far, several GPI-APs have been identified in the testicular germ cells, and there is increasing evidence of their biological significance during fertilization. Among GPI-APs identified [...] Read more.

Glycosylphosphatidylinositol (GPI)-anchored proteins (APs) on the plasma membrane are involved in several cellular processes, including sperm functions. Thus far, several GPI-APs have been identified in the testicular germ cells, and there is increasing evidence of their biological significance during fertilization. Among GPI-APs identified in the testis, this review focuses on TEX101, a germ cell-specific GPI-AP that belongs to the lymphocyte antigen 6/urokinase-type plasminogen activator receptor superfamily. This molecule was originally identified as a glycoprotein that contained the antigen epitope for a specific monoclonal antibody; it was produced by immunizing female mice with an allogenic testicular homogenate. This review mainly describes the current understanding of the biochemical, morphological, and physiological characteristics of TEX101. Furthermore, future avenues for the investigation of testicular GPI-Aps, including their potential role as regulators of ion channels, are discussed. Full article

(This article belongs to the Special Issue Ion Channels of Spermatozoa: Structure, Function and Regulation Mechanisms)

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