scholarly journals RNASET2 impairs the sperm motility via PKA/PI3K/calcium signal pathways

Reproduction ◽  
2018 ◽  
Vol 155 (4) ◽  
pp. 383-392 ◽  
Author(s):  
Yali Xu ◽  
Yong Fan ◽  
Weimin Fan ◽  
Jia Jing ◽  
Ke Xue ◽  
...  

Asthenozoospermia is one of the leading causes of male infertility owing to a decline in sperm motility. Herein, we determined if there is a correlation between RNASET2 content on human spermatozoa and sperm motility in 205 semen samples from both asthenozoospermia patients and normozoospermia individuals. RNASET2 content was higher in sperm from asthenozoospermia patients than in normozoospermia individuals. On the other hand, its content was inversely correlated with sperm motility as well as progressive motility. Moreover, the inhibitory effect of RNASET2 on sperm motility was induced by incubating normozoospermic sperm with RNase T2 protein. Such treatment caused significant declines in intracellular spermatozoa PKA activity, PI3K activity and calcium level, which resulted in severely impaired sperm motility, and the sperm motility was largely rescued by cAMP supplementation. Finally, protein immunoprecipitation and mass spectrometry identified proteins whose interactions with RNASET2 were associated with declines in human spermatozoa motility. AKAP4, a protein regulating PKA activity, coimmunoprecipated with RNASET2 and they colocalized with one another in the sperm tail, which might contribute to reduced sperm motility. Thus, RNASET2 may be a novel biomarker of asthenozoospermia. Increases in RNASET2 can interact with AKAP4 in human sperm tail and subsequently reduce sperm motility by suppressing PKA/PI3K/calcium signaling pathways.

Author(s):  
Naina Kumar ◽  
Amit Kant Singh

Abstract Sperms have attracted the attention of many researchers since it was discovered by Antonie van Leeuwenhoek in 1677. Though a small cell, its every part has complex structure and a different function to play in carrying life further. Sperm tail is the most complicated structure with more than 1000 proteins involved in its functioning. With advent of advanced three-dimensional microscopes, many studies are still undergoing to understand the exact mechanism of sperm tail movement. Most recent studies have shown that sperms move by spinning rather than swimming. Furthermore, each small subunit of tail including axonemal and peri-axonemal structures play essential roles in sperm motility, capacitation, hyperactivation, fertilization. Methodology: Relevant literature (from 1982 till 2020) on sperm tail anatomy, movement and functions were searched from various English language full length and review articles using PUBMED, SCOPUS or Google database. Conclusion: There is still a lot needed to be discovered about human sperm tail movement and its role in male fertility. Sperm tail has a complex anatomy with surrounding axoneme having 9+2 microtubules (9 outer doublet and one central doublet) arrangement along its entire length and additional peri-axonemal structures that all contribute in sperm motility and fertilization. In future various sperm tail proteins and its subunits can be used as markers of male fertility.


2020 ◽  
Author(s):  
Houyang Chen ◽  
Liang Tang ◽  
Qing Hong ◽  
Tingting Pan ◽  
Shiqi Weng ◽  
...  

Abstract STUDY QUESTION Is there an association between the human testis-specific gene, testis developmental related gene 1 (TDRG1) and human sperm motility? SUMMARY ANSWER TDRG1 is associated with asthenozoospermia and involved in regulating human sperm motility. WHAT IS KNOWN ALREADY Many testis-specific proteins potentially regulate spermatogenesis and sperm motility. We have identified a novel human testis-specific gene, TDRG1, which encodes a 100-amino-acid protein localized in the human sperm tail, yet little is known about its role in human spermatozoa. STUDY DESIGN, SIZE, DURATION Sperm samples were obtained from normozoospermic men and asthenozoospermic men who visited the reproductive medical center at Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China between February 2018 and January 2019. In total, 27 normozoospermic men and 25 asthenozoospermic men were recruited to participate in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS The level of TDRG1 in sperm of normozoospermic and asthenozoospermic men was examined by immunoblotting and immunofluorescence assays. Progressive motility was examined by computer-aided sperm analysis. The correlation between the TDRG1 protein level and progressive motility was analyzed by linear regression. TDRG1 was imported into the sperm of normozoospermic and asthenozoospermic men using a cell-penetrating peptide (CPP)-fused TDRG1 recombinant protein (CPP-TDRG1), and the progressive motility was examined. Also, the altered proteins associated with TDRG1 in asthenozoospermic sperm were detected using label-free quantification method-based quantitative proteomic technology. TDRG1-interacting proteins were identified by co-immunoprecipitation coupled with tandem mass spectrometry analysis. MAIN RESULTS AND THE ROLE OF CHANCE The mean level of TDRG1 was significantly decreased in sperm of asthenozoospermic men compared with normozoospermic men (P < 0.05) and was positively correlated with percentage of progressively motile sperm (r2 = 0.75, P = 0.0001). The introduction of TDRG1 into human sperm, using CPP, significantly increased progressive motility (P < 0.05) and improved the progressive motility of sperm from asthenozoospermic men to the normal level. TDRG1 forms a protein complex with sperm-motility related proteins in human sperm and its downregulation was associated with a decrease in other motility-related proteins. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION The sample size was limited and larger cohorts are needed for verifying the positive effect of CPP-TDRG1 on human sperm motility. Furthermore, the caution should be paid that a comprehensive safety examination would be performed to evaluate whether CPP-TDRG1 is a possible treatment approach for asthenozoospermia. WIDER IMPLICATIONS OF THE FINDINGS Our results provide new insights into the mechanisms of sperm motility which may contribute to the diagnosis and treatment for asthenozoospermia. STUDY FUNDING/COMPETING INTEREST(S) National Natural Science Foundation of China (81501317 and 81871207 to H.C.; 81771644 to T.L.; 31671204 to X.Z.; 81571432 to Y.T.). The authors have no conflicts of interest to declare.


2006 ◽  
Vol 91 (12) ◽  
pp. 4969-4975 ◽  
Author(s):  
Ekaitz Agirregoitia ◽  
Asier Valdivia ◽  
Arkaitz Carracedo ◽  
Luis Casis ◽  
Javier Gil ◽  
...  

Abstract Context: Endogenous opioid peptides signal through δ-, κ-, and μ-opioid receptors. Some of these peptides such as endorphins and enkephalins are present in the male reproductive tract, but the presence of the corresponding receptors in human sperm cells has not yet been reported. Objective: Our objective was to study the expression and localization of δ-, κ-, and μ-opioid receptors on human spermatozoa and the implication in sperm motility. Methods: The expression of receptors was studied by RT-PCR, Western blot, and immunofluorescence techniques. We evaluated the effects of activation of each opioid receptor by specific agonist and antagonist. Results: Human spermatozoa express δ-, κ-, and μ-opioid receptors. These receptors were located in different parts of the head, in the middle region, and in the tail of the sperm. Progressive motility of spermatozoa, an important parameter to evaluate male fertility, was found to be significantly reduced after incubation with the μ-receptor agonist morphine, whereas this effect was antagonized in the presence of the corresponding antagonist naloxone. The δ-receptor antagonist naltrindole significantly reduced progressive motility immediately after its addition. However, the δ-receptor agonist DPDPE had no significant effect. Finally, neither the κ-receptor agonist U50488 nor its antagonist nor-binaltorphimine significantly affected the progressive motility of human spermatozoa. Conclusion: We report for first time the presence of functional δ-, κ-, and μ-opioid receptors in human sperm membranes. These findings are indicative of a role for the opioid system in the regulation of sperm physiology.


2016 ◽  
Vol 28 (4) ◽  
pp. 434 ◽  
Author(s):  
Mariana Rios ◽  
Daniela V. Carreño ◽  
Carolina Oses ◽  
Nelson Barrera ◽  
Bredford Kerr ◽  
...  

Prostaglandins (PGs) have been reported to be present in the seminal fluid and cervical mucus, affecting different stages of sperm maturation from spermatogenesis to the acrosome reaction. This study assessed the effects of low physiological PGE2 and PGF2α concentrations on human sperm motility and on the ability of the spermatozoa to bind to the zona pellucida (ZP). Human spermatozoa were isolated from seminal samples with normal concentration and motility parameters and incubated with 1 μM PGE2, 1 μM PGF2α or control solution to determine sperm motility and the ability to bind to human ZP. The effects of both PGs on intracellular calcium levels were determined. Incubation for 2 or 18 h with PGE2 or PGF2α resulted in a significant (P < 0.05) increase in the percentage of spermatozoa with progressive motility. In contrast with PGF2α, PGE2 alone induced an increase in sperm intracellular calcium levels; however, the percentage of sperm bound to the human ZP was doubled for both PGs. These results indicate that incubation of human spermatozoa with low physiological levels of PGE2 or PGF2α increases sperm functions and could improve conditions for assisted reproduction protocols.


2018 ◽  
Vol 19 (3) ◽  
pp. 70-74
Author(s):  
V. V. Evdokimov ◽  
E. A. Efremov ◽  
P. A. Elistratov ◽  
I. A. Yamskov ◽  
A. F. Askerov ◽  
...  

The study objectiveis to examine the changes in motility of human spermatozoa under the effect of a protein-peptide complex extracted from cattle testes (Bos taurus).Materials and methods. The protein-peptide complex was extracted from testes tissue obtained during butchering of cattle at meat processing plants of the Moscow Region. Human spermatozoa were obtained from the ejaculate in the usual way. From the ejaculate sample, 1 ml was collected for the experiment and control. The protein-peptide complex was added to a test tube in concentrations of 10–8, 10–9, and  10–12 mg/ml. For every concentration, 10–12 experiments were performed. General and active motility were evaluated after 30 min, 1 and 3 hours of incubation at room temperature.Results and conclusion. The experiments have shown that in the presence of the protein-peptide complex, spermatozoa motility increased  by 10–30 % relative to the initial value at 30 minutes, and this change persisted for 3 hours of observation. The change depended on the complex concentration: the largest increase was observed at 10–12 mg/ml. Higher complex concentrations did not have a positive effect  on spermatozoa motility.


1987 ◽  
Vol 6 (5) ◽  
pp. 395-396 ◽  
Author(s):  
C.Y. Hong ◽  
C.C. Shieh ◽  
P. Wu ◽  
B.N. Chiang

The inhibitory effect of Old Coke, caffeine-free New Coke, New Coke, Diet Coke and Pepsi-Cola on human sperm motility was studied with a trans-membrane migration method. None of them could decrease sperm motility to less than 70% of control within one hour. A previous study which claimed a marked variation of spermicidal potencies among different formulations of Coca-Cola could not be confirmed. Even if cola has a spermicidal effect, its potency is relatively weak as compared with other well-known spermicidal agents.


Contraception ◽  
1986 ◽  
Vol 33 (3) ◽  
pp. 301-306 ◽  
Author(s):  
C.Y. Hong ◽  
J.J. Huang ◽  
B.N. Chiang ◽  
Y.H. Wei

Reproduction ◽  
2020 ◽  
Vol 159 (3) ◽  
pp. 241-249 ◽  
Author(s):  
Asier Valdivia ◽  
Lorea Cortés ◽  
Maider Beitia ◽  
Lide Totorikaguena ◽  
Naiara Agirregoitia ◽  
...  

Rennin-angiotensin system (RAS) has been involved in sperm function, even so, little is known about the implication of one of the RAS axis formed by Ang-(1–7) (angiotensin-(1–7)) and MAS receptor. Hence, in the present work, we focused on elucidating the function of the MAS receptor in human spermatozoa. We analyzed the expression and localization of MAS receptor in human spermatozoa and we observed if its activation is able to modulate the sperm motility of normal motility and/or asthenozoospermic patients, as well as, the acrosome reaction of the spermatozoa. MAS receptor is present in human mature spermatozoa, not only at the mRNA level but also at protein level. MAS is localized at the acrosome region, as well as, in the tail of spermatozoa. The sperm incubation with MAS agonist Ang-(1–7) activates at dose-dependent manner the PI3K/AKT pathway (P < 0.01 vs control) and improves the motility of asthenozoospermic patients (P < 0.01 vs control), which is blocked by the specific antagonist (A779) (P < 0.01), but it do not modulate the acrosome reaction. These findings suggest that the ACE2/Ang-(1–7)/Mas axis may be a useful biochemical tool for the treatment of male infertility related to sperm mobility.


1989 ◽  
Vol 8 (1) ◽  
pp. 49-51 ◽  
Author(s):  
C.Y. Hong ◽  
J.J. Huang ◽  
P. Wu

The inhibitory effect of gossypol acetic acid on human sperm motility was studied with a transmembrane migration method. Gossypol decreased sperm motility after it had been incubated with semen for more than 15 min. However, when sperm motility was evaluated immediately after semen had been mixed with gossypol, no inhibitory effect could be found. We consider that the sperm immobilizing potency of gossypol is much less than our previously studied sperm immobilizing agents. It is unlikely that gossypol can be developed as a vaginal spermicide. The importance of time course in the pharmacological study of sperm motility is emphasized in this study.


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