Testis developmental related gene 1 (TDRG1) encodes a progressive motility-associated protein in human spermatozoa

2020 ◽  
Author(s):  
Houyang Chen ◽  
Liang Tang ◽  
Qing Hong ◽  
Tingting Pan ◽  
Shiqi Weng ◽  
...  
Keyword(s):  
Sperm Motility ◽  
Conflicts Of Interest ◽  
Human Sperm ◽  
Human Spermatozoa ◽  
Mass Spectrometry Analysis ◽  
Human Testis ◽  
Specific Gene ◽  
Related Gene ◽  
Progressive Motility ◽  
Related Proteins

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.

scholarly journals Expression and Localization of δ-, κ-, and μ-Opioid Receptors in Human Spermatozoa and Implications for Sperm Motility

2006 ◽  
Vol 91 (12) ◽  
pp. 4969-4975 ◽  
Author(s):  
Ekaitz Agirregoitia ◽  
Asier Valdivia ◽  
Arkaitz Carracedo ◽  
Luis Casis ◽  
Javier Gil ◽  
...  
Keyword(s):  
Sperm Motility ◽  
Opioid Receptors ◽  
Receptor Agonist ◽  
Reproductive Tract ◽  
Human Sperm ◽  
Human Spermatozoa ◽  
Endogenous Opioid ◽  
Progressive Motility ◽  
Agonist And Antagonist ◽  
Μ Opioid Receptors

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.

Lysine glutarylation in human sperm is associated with progressive motility

2019 ◽  
Vol 34 (7) ◽  
pp. 1186-1194 ◽  
Author(s):  
Yi-min Cheng ◽  
Xiao-nian Hu ◽  
Zhen Peng ◽  
Ting-ting Pan ◽  
Fang Wang ◽  
...  
Keyword(s):  
Sperm Motility ◽  
Natural Science ◽  
Hot Spot ◽  
Human Sperm ◽  
Mature Sperm ◽  
Computer Assisted ◽  
Structured Illumination Microscopy ◽  
Progressive Motility ◽  
Wide Range

AbstractSTUDY QUESTIONIs there a role for lysine glutarylation (Kglu), a newly identified protein post-translational modification (PTM), in human sperm?SUMMARY ANSWERKglu occurs in several proteins located in the tail of human sperm, and it was reduced in asthenozoospermic (A) men and positively correlated with progressive motility of human sperm, indicating its important role in maintaining sperm motility.WHAT IS KNOWN ALREADYSince mature sperm are almost transcriptionally silent, PTM is regarded as an important pathway in regulating sperm function. However, only phosphorylation has been extensively studied in mature sperm to date. Protein lysine modification (PLM), a hot spot of PTMs, was rarely studied except for a few reports on lysine methylation and acetylation. As a newly identified PLM, Kglu has not been well characterized, especially in mature sperm.STUDY DESIGN, SIZE, DURATIONSperm samples were obtained from normozoospermic (N) men and A men who visited the reproductive medical center between February 2016 and January 2018. In total, 61 N men and 59 A men were recruited to participate in the study.PARTICIPANTS/MATERIALS, SETTING, METHODSKglu was examined by immunoblotting and immunofluorescence assays using a previously qualified pan-anti-glutaryllysine antibody that recognizes glutaryllysine in a wide range of sequence contexts (both in histones and non-histone substrates) but not the structurally similar malonyllysine and succinyllysine. The immunofluorescence assay was imaged using laser scanning confocal microscopy and super-resolution structured illumination microscopy. Sperm motility parameters were examined by computer-assisted sperm analysis.MAIN RESULTS AND THE ROLE OF CHANCEKglu occurs in several proteins (20–150 kDa) located in the tail of human sperm, especially in the middle piece and the latter part of the principal piece. Sperm Kglu was modulated by regulatory systems (enzymes and glutaryl-CoA) similar to those in HeLa cells. The mean level of sperm Kglu was significantly reduced in A men compared with N men (P < 0.001) and was positively correlated with progressive motility (P < 0.001). The sodium glutarate-induced elevation of Kglu levels in A men with lower Kglu levels in sperm significantly improved the progressive motility (P < 0.001). Furthermore, the reduced sperm Kglu levels in A men was accompanied by an increase in sperm glutaryl-CoA dehydrogenase (a regulatory enzyme of Kglu).LARGE SCALE DATAN/ALIMITATIONS, REASONS FOR CAUTIONAlthough the present study indicated the involvement of sperm Kglu in maintaining progressive motility of human sperm, the underlying mechanism needs to be investigated further.WIDER IMPLICATIONS OF THE FINDINGSThe findings of this study provide an insight into the novel role of Kglu in human sperm and suggest that abnormality of sperm PLMs may be one of the causes of asthenozoospermia.STUDY FUNDING/COMPETING INTEREST(S)National Natural Science Foundation of China (81 771 644 to T.L.; 31 671 204 to X.Z. and 81 871 207 to H.C.); National Basic Research Program of China (973 Program, 2015CB943003 to X.Z.); Natural Science Foundation of Jiangxi, China (20171ACB21006 and 20161BAB204167 to T.L.; 20165BCB18001 to X.Z.). The authors have no conflicts of interest to declare.

412 Searching for the Homologue Of The Human Testis-Specific Gene TDRG1 (Testis Developmental Related Gene 1) in Rhesus Macaque

2017 ◽  
Vol 14 (1) ◽  
pp. S126
Author(s):  
J. Yang ◽  
Y. Tang ◽  
H. Chen ◽  
H. Zhu ◽  
D. Li ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Human Testis ◽  
Specific Gene ◽  
Related Gene

scholarly journals Evaluation of the Efficiency of Two Different Freezing Media and Two Different Protocols to Preserve Human Spermatozoa from Cryoinjury

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Gemma Fabozzi ◽  
Maria Flavia Starita ◽  
Emilia Rega ◽  
Alessandra Alteri ◽  
Antonio Colicchia ◽  
...  
Keyword(s):  
Sperm Quality ◽  
Human Sperm ◽  
Human Spermatozoa ◽  
Sperm Cryopreservation ◽  
Progressive Motility ◽  
Direct Addition ◽  
Sperm Sample ◽  
Sperm Survival ◽  
Better Than

It is universally recognized that cryopreservation impairs sperm quality. In order to improve postthawing sperm survival and motility, media of different composition and different protocols have been proposed. However, no clear evidence is available to understand which are the most efficient protocol and medium for sperm cryopreservation. The present study evaluates the efficiency of two different cryopreservation protocols and two common freezing media (FM) containing different cryoprotectants (CPs), TEST Yolk Buffer (TYB) and Sperm Freeze (SF), to preserve human sperm quality. Our data suggest that TYB is better than SF both in terms of postthaw viability and in terms of progressive motility, while the direct addition of FM to the sperm sample resulted in the most efficient protocol in terms of postthaw viability but not in terms of progressive motility.

Low physiological levels of prostaglandins E2 and F2α improve human sperm functions

2016 ◽  
Vol 28 (4) ◽  
pp. 434 ◽  
Author(s):  
Mariana Rios ◽  
Daniela V. Carreño ◽  
Carolina Oses ◽  
Nelson Barrera ◽  
Bredford Kerr ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Sperm Motility ◽  
Acrosome Reaction ◽  
Seminal Fluid ◽  
Human Sperm ◽  
Human Spermatozoa ◽  
Control Solution ◽  
Prostaglandins E2 And F2α ◽  
Motility Parameters ◽  
Sperm Functions

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.

scholarly journals Characterization of a Novel Human Testis-Specific Gene: Testis Developmental Related Gene 1 (TDRG1)

2011 ◽  
Vol 225 (4) ◽  
pp. 311-318 ◽  
Author(s):  
Xianzhen Jiang ◽  
Dongjie Li ◽  
Jianfu Yang ◽  
Jiaming Wen ◽  
Houyang Chen ◽  
...  
Keyword(s):  
Human Testis ◽  
Specific Gene ◽  
Related Gene

Effect of temperature, nutrients, calcium, and cAMP on motility of human spermatozoa

1982 ◽  
Vol 242 (5) ◽  
pp. C304-C311 ◽  
Author(s):  
F. K. Gorus ◽  
R. Finsy ◽  
D. G. Pipeleers
Keyword(s):  
Seminal Fluid ◽  
Gradient Centrifugation ◽  
Cell Movement ◽  
Human Sperm ◽  
Correlation Spectroscopy ◽  
Human Spermatozoa ◽  
Effect Of Temperature ◽  
Dependent Manner ◽  
Calcium Dependent ◽  
Progressive Motility

The motility of human spermatozoa and its regulation were examined on cells isolated from other seminal components and purified into fractions of uniform progressive motility. The percent motile cells and estimates of their translational speed were determined by visual inspection, by stroboscopy, and by photon correlation spectroscopy; microcinematography and gradient centrifugation were occasionally used to clarify discrepancies. The motility of isolated spermatozoa could be maintained for periods up to 24 h at 4 or 37 degrees C; the presence of seminal fluid was not required and even provoked a reversible inhibition at 4 degrees C. Albumin facilitated cell movement between microscopic glass plates but had no effect on progressive motility per se, as evidenced by other techniques. During incubations of up to 2 h, progressive cell motility occurred independently of extracellular glucose and calcium but responded to variations in adenosine 3',5'-cyclic monophosphate and calcium. Dibutyryl cAMP increased forward motility, whereas ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid reversibly immobilized the spermatozoa in a calcium-dependent manner; phosphodiesterase inhibition resulted in increased vibration of sperm heads without any effect on progressive motility. Longer incubation periods required the presence of extracellular nutrients. These experiments further demonstrate that several motility measuring techniques should be used in parallel to distinguish the various components of cell movement, to exclude aspecific effects, and to supplement the shortcomings of each individual technique. Such procedure could clarify the various discrepancies that have been reported so far and should lead to a better understanding of the regulation of human sperm motility.

scholarly journals Human Sperm Motility, Viability, and Morphology Decreased after Cryopreservation

2019 ◽  
Vol 55 (3) ◽  
pp. 198
Author(s):  
Ninik Darsini ◽  
Berliana Hamidah ◽  
Seso Sulijaya Suyono ◽  
Faisal Yusuf Ashari ◽  
R Haryanto Aswin ◽  
...  
Keyword(s):  
Experimental Study ◽  
Informed Consent ◽  
Sperm Motility ◽  
Human Sperm ◽  
Sperm Viability ◽  
Group Design ◽  
Progressive Motility ◽  
Before And After ◽  
Immotile Spermatozoa ◽  
Fresh Semen

The aim of this study was to analyze human sperm motility, viability, and morphology before and after cryopreservation. This true laboratory experimental study had pre and post randomized one group design. The study was conducted at the Embryology, Andrology, and Genetics Laboratory, Department of Medical Biology, Faculty of Medicine, Universitas Airlangga from August to November 2017. The eighteen samples of fresh semen were collected from male volunteers who agreed and signed the informed consent of the study. Samples were analyzed their motility, viability, and morphology before and after cryopreservation. Results of this study indicated differentiation between motility before and after cryopreservation. Cryopreservation process decreased progressive motility (42.22 + 9.46%; 17.83 + 6.24%; p< 0.0001) and increased the number of immotile spermatozoa (35.44 + 10.15%; 60.11 + 12.53%; p< 0.0001). Cryopreservation also decreased human sperm viability (73.78 + 8.91%; 40.83 + 12.89%; p< 0.0001) and morphology (10.94 + 4.96%; 7.39 + 3.90%; p< 0.0001). Cryopreservation of human spermatozoa caused the decreased of motility, viability, and morphology.

scholarly journals Role of Angiotensin-(1–7) via MAS receptor in human sperm motility and acrosome reaction

Reproduction ◽  
2020 ◽  
Vol 159 (3) ◽  
pp. 241-249 ◽  
Author(s):  
Asier Valdivia ◽  
Lorea Cortés ◽  
Maider Beitia ◽  
Lide Totorikaguena ◽  
Naiara Agirregoitia ◽  
...  
Keyword(s):  
Sperm Motility ◽  
Acrosome Reaction ◽  
Mrna Level ◽  
Human Sperm ◽  
Human Spermatozoa ◽  
Dependent Manner ◽  
Mas Receptor ◽  
Sperm Mobility ◽  
Specific Antagonist

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.

Posttranslational lysine 2-hydroxyisobutyrylation of human sperm tail proteins affects motility

2020 ◽  
Vol 35 (3) ◽  
pp. 494-503
Author(s):  
Yi-min Cheng ◽  
Zhen Peng ◽  
Hou-yang Chen ◽  
Ting-ting Pan ◽  
Xiao-nian Hu ◽  
...  
Keyword(s):  
Sperm Motility ◽  
Natural Science ◽  
Human Sperm ◽  
Mature Sperm ◽  
Sperm Function ◽  
Sperm Tail ◽  
Progressive Motility ◽  
Penetration Ability ◽  
Tail Proteins

Abstract STUDY QUESTION Does lysine 2-hydroxyisobutyrylation, a newly identified protein posttranslational modification (PTM), occur in human sperm and affect human sperm function? SUMMARY ANSWER Lysine 2-hydroxyisobutyrylation mainly occurs in human sperm tail proteins, and excessive lysine 2-hydroxyisobutyrylation affects human sperm motility. WHAT IS KNOWN ALREADY PTM is regarded as an important pathway in regulating sperm function since mature sperm are almost transcriptionally silent. However, only phosphorylation was extensively studied in mature sperm to date. Lysine 2-hydroxyisobutyrylation, a newly characterised PTM, is broadly conserved in both eukaryotic and prokaryotic cells. Although histone lysine 2-hydroxyisobutyrylation has been shown to be associated with active gene expression in spermatogenic cells, the presence, regulatory elements and function of lysine 2-hydroxyisobutyrylation have not been characterised in mature sperm. STUDY DESIGN, SIZE, DURATION Sperm samples were obtained from normozoospermic men and asthenozoospermic men who visited the reproductive medical centre at Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, China, between May 2017 and November 2018. In total, 58 normozoospermic men and 65 asthenozoospermic men were recruited to participate in this study. PARTICIPANTS/MATERIALS, SETTING, METHODS Lysine 2-hydroxyisobutyrylation was examined using immunoblotting and immunofluorescence assays using a previously qualified pan anti-lysine 2-hydroxyisobutyrylation antibody. The immunofluorescence assay was imaged using super-resolution structured illumination microscopy. Sperm viability was examined by using the eosin staining method, and sperm motility parameters were assessed by computer-assisted sperm analysis. Sperm penetration ability was determined by evaluating the ability of the sperm to penetrate a 1% (w/v) methylcellulose solution. The level of intracellular adenosine triphosphate (ATP) was detected using a rapid bioluminescent ATP assay kit. MAIN RESULTS AND THE ROLE OF CHANCE Lysine 2-hydroxyisobutyrylation was present in several proteins (20–100 kDa) mainly located in the tail of human sperm. Sperm lysine 2-hydroxyisobutyrylation was derived from 2-hydroxyisobutyrate (2-Hib) and was regulated by acyltransferase P300 and nicotinamide adenine dinucleotide-dependent lysine deacylase sirtuins. Elevation of sperm lysine 2-hydroxyisobutyrylation by 2-Hib decreased total motility, progressive motility, penetration ability and ATP level of human sperm. Interestingly, the level of sperm lysine 2-hydroxyisobutyrylation was higher in asthenozoospermic men than that in normozoospermic men and was negatively correlated with the progressive motility of human sperm. Furthermore, high levels of lysine 2-hydroxyisobutyrylation in asthenozoospermic men accompanied decreased ATP levels. LIMITATIONS, REASONS FOR CAUTION Although the present study indicated the involvement of sperm lysine 2-hydroxyisobutyrylation in regulating human sperm motility, the underlying mechanism needs to be further illustrated. WIDER IMPLICATIONS OF THE FINDINGS The findings of this study provide insight into the novel role of lysine 2-hydroxyisobutyrylation in human sperm and suggest that abnormality of sperm lysine 2-hydroxyisobutyrylation may be one of the causes for asthenozoospermia. STUDY FUNDING/COMPETING INTEREST(S) National Natural Science Foundation of China (81771644 to T.L. and 81871207 to H.C.); Natural Science Foundation of Jiangxi province (20171ACB21006). The authors have no conflicts of interest to declare.

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