Participation of the inositol 1,4,5-trisphosphate-gated calcium channel in the zona pellucida- and progesterone-induced acrosome reaction and calcium influx in human spermatozoa

Li, Yingya; Jia, Yanping; Duan, Liyan

doi:10.4103/aja.aja_44_19

Cited by 11 publications

(11 citation statements)

References 6 publications

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“…Previous studies also showed that Tyr-P decreased in the presence of either specific inhibitors of CFTR, or blockers of the Na/HCO 3 cotransporter (NBC) and Na-channels (ENaCs) [9,24], corroborating the notion of a strong relationship between bicarbonate entry and phosphorylation in capacitation. The eAE1 exchanger activity is up-regulated by casein kinase 2-dependent phosphorylation of the serine residues in the cytoplasmic domain of the protein [35][36][37], whereas the phosphorylation of its tyrosine residues affects the interactions with other proteins and enzymes [15,16].…”

Section: Discussionmentioning

confidence: 53%

“…Previous studies showed that specific inhibitors of CFTR and the Na/HCO 3 − cotransporter (NBC), or the epithelial Na-channels (ENaCs) blockers [9,24] inhibited flagellar movements, capacitation and AR, but also reduced the extent of Tyr-P, implying a role of bicarbonate in sperm Tyr-P.…”

Section: Discussionmentioning

confidence: 99%

“…The calcium ionophore (A23187)-mediated calcium increase activates phospholipase C (PLC), generating inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 and DAG THEN act as second messengers to activate IP3 receptor (IP3R) and protein kinase C, both involved in the AR regulation [24]. However, the identification of proteins modulating and undergoing phosphorylation processes is still incomplete.…”

Section: Hcomentioning

confidence: 99%

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Human Sperm Capacitation Involves the Regulation of the Tyr-Phosphorylation Level of the Anion Exchanger 1 (AE1)

Donà

Tibaldi

Andrisani

et al. 2020

IJMS

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Bicarbonate uptake is one of the early steps of capacitation, but the identification of proteins regulating anion fluxes remains elusive. The aim of this study is to investigate the role of sperm solute carrier 4 (SLC4) A1 (spAE1) in the capacitation process. The expression, location, and tyrosine-phosphorylation (Tyr-P) level of spAE1 were assessed. Thereby, it was found that 4,4′-Diisothiocyano-2,2′-stilbenedisulfonic acid (DIDS), an SLC4 family channel blocker, inhibited capacitation in a dose-dependent manner by decreasing acrosome reaction (ARC% 24.5 ± 3.3 vs. 64.9 ± 4.3, p < 0.05) and increasing the percentage of not viable cells (NVC%), comparable to the inhibition by I-172, a cystic fibrosis transmembrane conductance regulator (CFTR) blocker (AR% 30.5 ± 4.4 and NVC% 18.6 ± 2.2). When used in combination, a synergistic inhibitory effect was observed with a remarkable increase of the percentage of NVC (45.3 ± 4.1, p < 0.001). spAE1 was identified in sperm membrane as a substrate for Tyr-protein kinases Lyn and Syk, which were identified as both soluble and membrane-bound pools. spAE1-Tyr-P level increased in the apical region of sperm under capacitating conditions and was negatively affected by I-172 or DIDS, and, to a far greater extent, by a combination of both. In conclusion, we demonstrated that spAE1 is expressed in sperm membranes and it is phosphorylated by Syk, but above all by Lyn on Tyr359, which are involved in sperm viability and capacitation.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Hcomentioning

confidence: 99%

See 1 more Smart Citation

Human Sperm Capacitation Involves the Regulation of the Tyr-Phosphorylation Level of the Anion Exchanger 1 (AE1)

Donà

Tibaldi

Andrisani

et al. 2020

IJMS

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“…The specimen used for capacitation status and acrosome reaction determination required isolation of highly motile spermatozoa by the swim‐up protocol in EBSS/3%BSA (supplemented with 0.265 mg/mL calcium chloride, 0.033 mg/mL sodium pyruvate, 1% (v/v) penicillin‐streptomycin, and 3% (w/v) BSA) at 37°C in an atmosphere of 5% CO 2 in air for 1 hour. Next, highly motile spermatozoa were incubated with EBSS/3% BSA for 3 hours for capacitation 32 …”

Section: Methodsmentioning

confidence: 99%

Supplementation of cryoprotectant withPinus massonianabark extract improves human sperm vitality and fertility potential

Zhang

Jia

et al. 2020

Andrology

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Background Sperm cryopreservation is commonly used to preserve fertility but often decreases sperm quality by inducing oxidative stress. Pinus massoniana bark extract (Pinus massoniana, PMBE) exhibits strong antioxidant activity and has been used in traditional Chinese medicine. Objectives The objective was to determine whether adding PMBE to cryoprotectant could improve human sperm quality after cryo‐resuscitation and to investigate the potential regulatory mechanisms. Methods PMBE was used as a cryoprotectant supplement. Hydrogen peroxide was applied to generate oxidative stress. The changes in sperm quality upon cryo‐resuscitation and hydrogen peroxide treatment were measured by computer‐aided sperm analysis and fluorescein isothiocyanate‐labeled peanut (Pisum sativum) agglutinin staining. Oxidative stress was evaluated by dichlorofluorescein diacetate staining and the malondialdehyde content. The antioxidant capacity was determined by the glutathione peroxidase activity and the reduced glutathione content. Mass spectrometry was utilized to screen factors potentially regulated by PMBE, and the screened factors were evaluated by Western blot. Mouse in vitro fertilization was used to assess the effectiveness and safety of PMBE on the fertilization outcome of damaged spermatozoa. Results PMBE addition to cryoprotectant could effectively promote post‐thaw vitality and acrosome reaction rates, reduce intracellular reactive oxygen species, and preserve antioxidant capacity and mitochondrial function in the presence of cryo‐resuscitation and hydrogen peroxide treatment. Decreased in the expression of critical proteins such as inositol‐3‐phosphate synthase 1 (ISYNA1) and AKT1 upon resuscitation was rescued by PMBE supplementation, further reducing the cytoplasmic Nrf2 protein level and markedly increasing the nuclear level. PMBE dramatically enhanced the mRNA and protein expression of superoxide dismutase (SOD2). PMBE effectively alleviated the hydrogen peroxide‐induced decline in the two‐cell embryo rates. Conclusion Supplementing cryoprotectant with PMBE improves human sperm quality after cryo‐resuscitation by reducing oxidative stress and stabilizing the functional proteins ISYNA1 and AKT1. PMBE addition improves the fertilization outcome of oxidative stress‐damaged spermatozoa.

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“…IP3R is thought to be involved in sperm hyperactivation [42,54] and the regulation of thermotaxis [55]. A recent study using a novel permeabilization tool, BioPORTER, to deliver IP3R antibody or IP3 to block or activate IP3R activity, respectively, showed that the IP3R1 channel was involved in the zona pellucida-and progesterone-induced acrosome reaction and calcium influx [56]. These pharmacological or in vitro findings indicated that the IP3R channel is vital for the regulation of spermatogenesis and mature sperm function.…”

Section: Roles Of Ip3r In Male Reproductionmentioning

confidence: 97%

IP3R Channels in Male Reproduction

Zhang

Huang

Zhou

et al. 2020

IJMS

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As a second messenger in cellular signal transduction, calcium signaling extensively participates in various physiological activities, including spermatogenesis and the regulation of sperm function. Abnormal calcium signaling is highly correlated with male infertility. Calcium signaling is mainly regulated by both extracellular calcium influx and the release of calcium stores. Inositol 1,4,5-trisphosphate receptor (IP3R) is a widely expressed channel for calcium stores. After being activated by inositol 1,4,5-trisphosphate (IP3) and calcium signaling at a lower concentration, IP3R can regulate the release of Ca2+ from stores into cytoplasm, and eventually trigger downstream events. The closure of the IP3R channel caused by a rise in intracellular calcium signals and the activation of the calcium pump jointly restores the calcium store to a normal level. In this review, we aim to discuss structural features of IP3R channels and the underlying mechanism of IP3R channel-mediated calcium signaling and further focus on the research progress of IP3R expression and function in the male reproductive system. Finally, we propose key directions and strategies for research of IP3R in spermatogenesis and the regulation of sperm function to provide more understanding of the function and mechanism of IP3R channel actions in male reproduction.

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Participation of the inositol 1,4,5-trisphosphate-gated calcium channel in the zona pellucida- and progesterone-induced acrosome reaction and calcium influx in human spermatozoa

Cited by 11 publications

References 6 publications

Human Sperm Capacitation Involves the Regulation of the Tyr-Phosphorylation Level of the Anion Exchanger 1 (AE1)

Human Sperm Capacitation Involves the Regulation of the Tyr-Phosphorylation Level of the Anion Exchanger 1 (AE1)

Supplementation of cryoprotectant withPinus massonianabark extract improves human sperm vitality and fertility potential

IP3R Channels in Male Reproduction

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