scholarly journals 216.The effects of Viagra on sperm function and early embryo development

2004 ◽  
Vol 16 (9) ◽  
pp. 216
Author(s):  
S. E. M. Lewis ◽  
D. R. J. Glenn ◽  
N. McClure
Keyword(s):  
Semen Analysis ◽  
Plasma Concentrations ◽  
Phosphodiesterase Inhibitor ◽  
Fluorescein Isothiocyanate ◽  
Human Sperm ◽  
Blastocyst Stage ◽  
Early Embryo ◽  
Computer Assisted ◽  
Sperm Function ◽  
Embryo Cleavage

In an audit of UK fertility units, we have demonstrated that 42% prescribe Viagra to aid patient semen production. Viagra is a phosphodiesterase inhibitor (PDE5) and as non-specific PDEs have been shown to affect fertility, safety concerns have been raised. The aims of this study are to investigate the effects of Viagra on sperm function and early embryo cleavage. Human semen was incubated with and without Viagra (450�ng/mL sildenafil citrate, equivalent to plasma concentrations after 100�mg oral dose; Pfizer, UK). Aliquots were also prepared by a 90/45% density centrifugation gradient to separate good and poor subpopulations. All samples were analysed by computer assisted semen analysis (HTM-IVOS) up to 60 and 120�min. Prepared samples were also labelled with fluorescein isothiocyanate–peanut agglutinin to determine acrosome status. Male mice were gavaged with Viagra (equivalent dose/body wt) and mated with superovulating females. Twenty females were sacrificed 12�h later, their oviducts flushed and viable fertilized oocytes counted. Another 20 females were sacrificed 4�days after mating and their embryo numbers and cleavage stages determined. Viagra increased % progressive motility in semen (n�=�22) by 38%, VAP by 21%, VSL by 21% and VCL by 16% at 60�min (all P values <0.001). These effects were sustained at 120�min. Sperm isolated from 90% (n�=�57) and 45% (n�=�15) fractions showed similar increases. Viagra also increased the proportion of acrosome reacted sperm in the 90% (+79%, P�<�0.001) and 45% (+77%, P�<�0.001) fractions. Further, Viagra caused a reduction in both the numbers of fertilised oocytes (–35%, P�<�0.001) and those reaching blastocyst stage (85%, P�<�0.001). This study demonstrates that Viagra increases human sperm motility. However, Viagra induces human premature acrosome reactions and impairs mouse fertilisation and embryo cleavage. This study raises significant concerns for its use in assisted reproduction.

scholarly journals Myeloperoxidase inhibitor AZD5904 enhances human sperm function in vitro

2021 ◽  
Author(s):  
M J Campbell ◽  
I E Sucquart ◽  
A Whittaker ◽  
H J Sanganee ◽  
C L R Barratt ◽  
...  
Keyword(s):  
Male Infertility ◽  
Sperm Motility ◽  
In Vitro Model ◽  
Semen Analysis ◽  
Human Sperm ◽  
Computer Assisted ◽  
Sperm Function ◽  
Sperm Penetration ◽  
Vitro Model

Abstract STUDY QUESTION Does AZD5904, a myeloperoxidase inhibitor (MPOi), have any effect on human sperm function in vitro? SUMMARY ANSWER AZD5904 improves sperm function in an in vitro model of oxidative stress (OS) and potentially offers a novel treatment approach for male infertility. WHAT IS KNOWN ALREADY Male infertility is an underlying or contributory cause in half of all couples experiencing difficulties conceiving, yet there is currently no effective treatment or cure. OS is a common pathology in a significant proportion of infertile men. It can negatively affect sperm motility and the ability to fertilize a mature oocyte, as well as DNA integrity, and therefore represents an attractive target for therapeutic intervention. STUDY DESIGN, SIZE, DURATION This study included population-based samples from men (23–50 years) attending Ninewells Assisted Conception Unit, Dundee for diagnostic semen analysis, July 2017–September 2018. Semen samples (n = 47) from 45 patients were used. PARTICIPANTS/MATERIALS, SETTING, METHODS Neutrophils activated using zymosan were incubated with prepared human spermatozoa for 2 h (T2) and 24 h (T24) to create an in vitro model of OS. Parallel samples were co-incubated with AZD5904, an MPOi, to examine its effects. Sperm motility was assessed by computer-assisted sperm analysis at T2 and T24. Functional motility was assessed by sperm penetration assay. Statistical analysis was performed using GraphPad Prism. MAIN RESULTS AND THE ROLE OF CHANCE There was no significant difference in total or progressive sperm motility between any treatment and control groups at T2 or T24. Nonetheless, significant positive effects on sperm function were observed with AZD5904, with 16/45 (35.6%) samples (with both normal and abnormal baseline semen analysis characteristics) displaying a ≥20% increase in sperm penetrated through viscous media (P &lt; 0.003). LIMITATIONS, REASONS FOR CAUTION This was an in vitro study. WIDER IMPLICATIONS OF THE FINDINGS Treatment with AZD5904 resulted in significant increased sperm penetration in one of three samples treated, which is likely to represent improvement in sperm function required for fertilization. We are now planning a clinical trial to validate these results and hope that this could represent a new treatment for male infertility. STUDY FUNDING/COMPETING INTEREST(S) AZD5904 was shared through the AstraZeneca Open Innovation program. The study was funded by AstraZeneca and sponsored by the University of Dundee. Additional funding was provided by Chief Scientist Office/NHS Research Scotland (S.J.M.d.S.). A.W. and H.J.S. are both full time employees of AstraZeneca. A.W. and H.J.S. are inventors on a patent filed by AstraZeneca titled MPOi for use in medicine which includes MPOi for use in the treatment of male infertility (WO 2019/016074 Al). S.J.M.d.S. is Associate Editor of Human Reproduction and Editorial Board member of Reproduction & Fertility. C.L.R.B. is Editor of RBMO and has received lecturing fees from Merck and Ferring and is on the Scientific Advisory Panel for Ohana BioSciences. C.L.R.B. was chair of the World Health Organization Expert Synthesis Group on Diagnosis of Male infertility (2012–2016). C.L.R.B. has a patent WO2013054111 A1 issued. The other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

scholarly journals Evidence of 5-HT components in human sperm: implications for protein tyrosine phosphorylation and the physiology of motility

Reproduction ◽  
2012 ◽  
Vol 144 (6) ◽  
pp. 677-685 ◽  
Author(s):  
Francisco Jiménez-Trejo ◽  
Miguel Tapia-Rodríguez ◽  
Marco Cerbón ◽  
Donald M Kuhn ◽  
Gabriel Manjarrez-Gutiérrez ◽  
...  
Keyword(s):  
Western Blot ◽  
Enzymatic Activity ◽  
Tyrosine Phosphorylation ◽  
Sperm Motility ◽  
Tryptophan Hydroxylase ◽  
Semen Analysis ◽  
Human Sperm ◽  
Computer Assisted ◽  
Serotoninergic System ◽  
Peripheral Tissues

Serotonin (5-hydroxytryptamine; C10H12N2O (5-HT)) is produced in the CNS and in some cells of peripheral tissues. In the mammalian male reproductive system, both 5-HT and tryptophan hydroxylase (TPH) have been described in Leydig cells of the testis and in principal cells of the caput epididymis. In capacitated hamster sperm, it has been shown that 5-HT promotes the acrosomal reaction. The aim of this work was to explore the existence of components of the serotoninergic system and their relevance in human sperm physiology. We used both immunocytochemistry and western blot to detect serotoninergic markers such as 5-HT, TPH1, MAOA, 5-HT1B, 5-HT3, and 5HTT; HPLC for TPH enzymatic activity; Computer Assisted Semen Analysis assays to measure sperm motility parameters and pharmacological approaches to show the effect of 5-HT in sperm motility and tyrosine phosphorylation was assessed by western blot. We found the presence of serotoninergic markers (5-HT, TPH1, MAOA, 5-HT1B, 5-HT2A, 5-HT3, 5-HTT, and TPH enzymatic activity) in human sperm. In addition, we observed a significant increase in tyrosine phosphorylation and changes in sperm motility after 5-HT treatment. In conclusion, our data demonstrate the existence of components of a serotoninergic system in human sperm and support the notion for a functional role of 5-HT in mammalian sperm physiology, which can be modulated pharmacologically.

scholarly journals Capacitation-associated protein tyrosine phosphorylation and membrane fluidity changes are impaired in the spermatozoa of asthenozoospermic patients

Reproduction ◽  
2005 ◽  
Vol 129 (6) ◽  
pp. 697-705 ◽  
Author(s):  
Mariano G Buffone ◽  
Juan C Calamera ◽  
Sandra V Verstraeten ◽  
Gustavo F Doncel
Keyword(s):  
Membrane Fluidity ◽  
Tyrosine Phosphorylation ◽  
Plasma Membranes ◽  
Phosphodiesterase Inhibitor ◽  
Human Sperm ◽  
Computer Assisted ◽  
Protein Tyrosine Phosphorylation ◽  
Membrane Composition ◽  
Protein Tyrosine ◽  
Camp Analog

Sperm protein tyrosine phosphorylation has been associated with capacitation, motility changes, zona binding, and fertilizing ability. We previously demonstrated that gradient-isolated human sperm subpopulations differ in their plasma membrane composition, their ability to phosphorylate proteins in tyrosine residues, and their capacity to undergo hyperactivation. In this study, we have characterized capacitation-associated changes in protein tyrosine phosphorylation and membrane fluidity in spermatozoa of asthenozoospermic and normozoospermic patients consulting for infertility. Semen samples were studied at baseline and after a capacitating incubation with or without the addition of a permeable cAMP analog and a phosphodiesterase inhibitor. Basic sperm and computer-assisted motion parameters, hyperactivation, protein tyrosine phosphorylation (immunofluorescence and Western blot), and membrane fluidity (fluorescent Laurdan probe) were the main study parameters. In comparison with normozoospermic and proven-fertile donor semen, asthenozoospermic samples showed lower motility, velocity, and amplitude of lateral head displacement, both originally and after a 6-h capacitating incubation. Unlike those in normal samples, asthenozoospermic spermatozoa were unable to increase protein tyrosine phosphorylation during capacitation. Such impairment, however, was overcome when they were incubated with a membrane-permeable cAMP analog and a phosphodiesterase inhibitor, indicating a possible membrane defect. Confirming this hypothesis, plasma membranes of asthenozoospermic sperm showed decreased fluidity (increased Laurdan polarization), even after a capacitating incubation. In conclusion, spermatozoa from functional asthenozoospermic samples may owe their poor motility, and their inability to properly capacitate and develop hyperactivation, to an impairment in the tyrosine phosphorylation of critical proteins caused by decreased membrane fluidity. These findings suggest a molecular pathogenetic mechanism for a common seminal pathology associated with male infertility.

225 DOES THE SUPPLEMENTATION OF THE BOAR SEMEN EXTENDER WITH CARNOSINE, L-HISTIDINE, AND TAURINE PRESERVE SPERM FUNCTION DURING STORAGE?

2008 ◽  
Vol 20 (1) ◽  
pp. 192
Author(s):  
C. Matás ◽  
J. C. Gardón ◽  
F. A. Garcia-Vazquez ◽  
S. Pacchini ◽  
M. Ducci
Keyword(s):  
Sperm Motility ◽  
Membrane Lipids ◽  
Semen Analysis ◽  
Antioxidant Systems ◽  
Ros Generation ◽  
Computer Assisted ◽  
Sperm Function ◽  
Taurine Supplementation ◽  
Boar Semen ◽  
Motility Parameters

High levels of reactive oxygen species (ROS: superoxide, hydroxyl, hydrogen peroxide, nitric oxide, peroxynitrile) endanger sperm motility, viability, and function by interaction with membrane lipids, proteins, and nuclear and mitochondrial DNA (Sikka 2004 J. Androl. 25, 5–18). ROS generation has a significant negative effect on the fertilization rate after IVF, and so measurement of ROS levels in semen specimens before IVF may be useful in predicting the IVF outcome (Agarwal et al. 2005 Fertil. Steril. 84, 228–231). Several compounds of the antioxidant systems have been identified in the epididymal environment, spermatozoa, and seminal plasma. The antioxidants carnosine, L-histidine (Ducci et al. 2006 Pol. J. Vet. Sci. 9, 159–163), and taurine (Van der Horst and Grooten 1966 Biochim. Biophys. Acta. 117, 495–497) have been detected in boar semen and added to the extender in freezing procedures in several species. The main objective of this study was to evaluate the effect of carnosine, L-histidine, and taurine supplementation of the extender on boar sperm functionality as measured by sperm motility during computer-assisted semen analysis (CASA) and by IVF ability using mature oocytes, as previously described (Selles et al. 2003 Reprod. Domest. Anim. 38, 66–72). The sperm-rich fraction from mature fertile boars was diluted with isothermal Beltsville thawing solution (BTS) extender. Diluted semen was placed at 15�C and centrifuged at 800g for 10 min. The semen pellet was resuspended with BTS supplemented by 5 mm of carnosine, L-histidine, or taurine or not supplemented (control) to provide 75 � 106 spermatozoa mL–1 and stored at 15�C for 24 h (IVF assay), or 48 or 120 h (for CASA assay). We observed that the motility parameters were affected by storage time and that the addition of taurine increased the motility at 48 h of storage. Alternately, the addition of L-histidine to the extender reduced significantly the motility parameters after 120 h. The results showed that the addition of L-histidine induced a significant (P ≤ 0.01) decrease of the penetration rate (L-histidine 75.8% v. control 89.9%) and the number of sperm per oocyte penetrated (L-histidine 3.1 v. control 4.1). The rate of male pronuclear formation was not affected by the addition of antioxidants to the extender (over 85% in all cases). The addition of carnosine and taurine had no effect on the IVF parameters. In conclusion the antioxidants carnosine, taurine, and L-histidine affect sperm functionality differently, and further studies are necessary to elucidate what changes in sperm function take place during storage and the mechanisms by which these antioxidants exert their effects. This work was supported by Italian-Spanish research project HI2005-0165 and AGL2006-03495.

scholarly journals ATPases, ion exchangers and human sperm motility

Reproduction ◽  
2015 ◽  
Vol 149 (5) ◽  
pp. 475-484 ◽  
Author(s):  
Rubén D Peralta-Arias ◽  
Carmen Y Vívenes ◽  
María I Camejo ◽  
Sandy Piñero ◽  
Teresa Proverbio ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Atpase Activity ◽  
Sperm Motility ◽  
Plasma Membranes ◽  
Semen Analysis ◽  
Human Sperm ◽  
The Other ◽  
Computer Assisted ◽  
Acidic Ph ◽  
Α Subunit

Human sperm has several mechanisms to control its ionic milieu, such as the Na,K-ATPase (NKA), the Ca-ATPase of the plasma membrane (PMCA), the Na+/Ca2+-exchanger (NCX) and the Na+/H+-exchanger (NHE). On the other hand, the dynein-ATPase is the intracellular motor for sperm motility. In this work, we evaluated NKA, PMCA, NHE, NCX and dynein-ATPase activities in human sperm and investigated their correlation with sperm motility. Sperm motility was measured by Computer Assisted Semen Analysis. It was found that the NKA activity is inhibited by ouabain with twoKi(7.9×10−9and 9.8×10−5 M), which is consistent with the presence of two isoforms of α subunit of the NKA in the sperm plasma membranes (α1 and α4), being α4 more sensitive to ouabain. The decrease in NKA activity is associated with a reduction in sperm motility. In addition, sperm motility was evaluated in the presence of known inhibitors of NHE, PMCA and NCX, such as amiloride, eosin, and KB-R7943, respectively, as well as in the presence of nigericin after incubation with ouabain. Amiloride, eosin and KB-R7943 significantly reduced sperm motility. Nigericin reversed the effect of ouabain and amiloride on sperm motility. Dynein-ATPase activity was inhibited by acidic pH and micromolar concentrations of Ca2+. We explain our results in terms of inhibition of the dynein-ATPase in the presence of higher cytosolic H+and Ca2+, and therefore inhibition of sperm motility.

scholarly journals β-Elemene Inhibits Human Sperm Function by Affecting Sperm Vitality and Intracellular Calcium

2018 ◽  
Vol 51 (5) ◽  
pp. 2019-2029 ◽  
Author(s):  
Wen Chen ◽  
Shi-qi Weng ◽  
Meng-ge Lv ◽  
Wen-qiong Chen ◽  
Zhuo-fei Bi ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Acrosome Reaction ◽  
A549 Cells ◽  
Human Sperm ◽  
Underlying Mechanism ◽  
Computer Assisted ◽  
Sperm Function ◽  
Dependent Manner ◽  
Sperm Analysis

Background/Aims: β-Elemene is a bioactive sesquiterpene compound that exhibits a potent anti-tumor effect and is used in various clinical applications. However, little is known about its effect on the male reproductive system. The objective of this study was to investigate the in vitro actions of β-elemene on human sperm function and elucidate the underlying mechanism. Methods: The cytotoxicity of β-elemene toward MCF-10A, MDA-MD-231, and A549 cells was evaluated with cell proliferation and colony formation assays. Additionally, human sperm were treated with different concentrations (0, 10, 20, 40, 80, 160, and 320 µM) of β-elemene in vitro. The characteristics in human sperm essential for fertilization, including vitality, motility, capacitation, acrosome reaction, responsiveness to progesterone, and intracellular calcium concentration ([Ca2+]i) were examined with a computer-assisted sperm analysis system, chlortetracycline staining, and a fluorescent Ca2+ indicator. Results: A comprehensive evaluation of sperm motility, especially hyperactivated motility, revealed that treatments with 40–320 μM β-elemene decreased human sperm vitality, motility (total motility, progressive motility, and curvilinear velocity), and penetrating ability in a dose-dependent manner, but were non-toxic or minimally toxic toward MCF-10A, MDA-MD-231, and A549 cells. Although 10 and 20 μM β-elemene did not affect sperm vitality and motility, these concentrations increased the spontaneous acrosome reaction and inhibited progesterone-induced sperm functions by affecting sperm [Ca2+]i. Conclusion: These results suggest that β-elemene inhibits human sperm function by affecting sperm vitality and [Ca2+]i. These observations must be considered when using β-elemene to treat cancer patients who may wish to preserve their fertility.

scholarly journals Impact of Seminal Plasma Trace Elements on Human Sperm Motility Parameters

2018 ◽  
Vol 56 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Mohammad Mostakhdem Hashemi ◽  
Nasser Behnampour ◽  
Mojgan Nejabat ◽  
Afsaneh Tabandeh ◽  
Behrouz Ghazi-Moghaddam ◽  
...  
Keyword(s):  
Trace Elements ◽  
Sperm Motility ◽  
Seminal Plasma ◽  
Sperm Quality ◽  
Semen Analysis ◽  
Sperm Concentration ◽  
Negative Relationship ◽  
Human Sperm ◽  
Computer Assisted ◽  
Human Seminal Plasma

Abstract Introduction. Human seminal plasma contains a variety of macro and trace elements including magnesium (Mg), copper (Cu), zinc (Zn), and iron (Fe) that have essential roles in normal functioning of semen and its quality. The imbalance of these elements has been reported in several pathologic and male infertility disorders. Therefore, this study aimed to determine the levels of these elements in seminal plasma samples, their relationships with each other and their impact on sperm motility. Methods. Overall, 192 males (96 normospermic and 96 asthenospermic males) were enrolled in the study. Semen samples were collected by masturbation and computer-assisted/aided semen analysis of sperm motility was performed. The samples were centrifuged and seminal levels of Mg, Cu, Zn and Fe were measured using atomic absorption spectroscopy. Results. The levels of Zn did not differ between the two groups, while the levels of Mg, Cu, and Fe were significantly higher in normospermic males. Fe showed a positive correlation with Mg and Cu in asthenospermic group. However, a negative relationship was found between Mg and Fe levels and between Mg and sperm concentration in the normospermic group. Fe levels were higher in the normospermic group compared to the asthenospermic group. Nevertheless, increased Fe levels caused a decrease in most of sperm motility fractions. Conclusion: Elements play major roles in male fertility and directly affect sperm quality. According to the results of this study, the levels of Zn do not affect the sperm quality and motility, while Fe, Cu and Mg are decreased in males with sperm motility problems. Nevertheless, Fe levels can adversely affect sperm motility in normospermic men.

66 EFFECT OF ADDITION OF CHOLESTEROL-LOADED CYCLODEXTRIN BEFORE FREEZING ON QUALITY AND FERTILITY OF STALLION FROZEN SEMEN

2015 ◽  
Vol 27 (1) ◽  
pp. 126
Author(s):  
F. O. Papa ◽  
C. Ramires Neto ◽  
Y. F. R. Sancler-Silva ◽  
H. L. Resende ◽  
G. A. Monteiro ◽  
...  
Keyword(s):  
Kinetic Parameters ◽  
Semen Analysis ◽  
Membrane Integrity ◽  
Skim Milk ◽  
Fluorescein Isothiocyanate ◽  
Treated Group ◽  
Control Group ◽  
Computer Assisted ◽  
Exact Test ◽  
Frozen Semen

The aim of the present study was to evaluate the effect of cholesterol-loaded cyclodextrin on the quality and fertility of stallion frozen semen. Three ejaculates from each of 4 stallions were used. The semen was diluted (1 : 1) with a skim milk-based extender (Botu-SemenTM, Botupharma, Brazil). The samples were divided into 2 groups: control group (CG), composed of semen diluted only with extender, and treated group (TG), composed of semen diluted with extender plus 750 mg mL–1 of cholesterol-loaded cyclodextrin. Both groups were incubated for 15 min at 20°C. The semen was frozen with Botu-CryoTM (Botupharma, Brazil) extender according to the manufacturer's protocol in 0.5-mL straws containing 100 × 106 of total sperm. The sperm kinetic parameters were analysed by computer-assisted semen analysis, and plasma membrane integrity by flow cytometer (propidium iodide and fluorescein isothiocyanate -PSA) on post-thaw. The fertility trial was carried out inseminating 2 cycles of 20 mares (total of 40 cycles) immediately post-ovulation using 4 straws of CG or TG (400 × 106 total sperm), one from each stallion in a randomised design. Comparison of sperm parameters was performed by t-test and fertility by Fisher's exact test. No difference (P > 0.05) was observed in total motility (%, CG = 57.9 ± 6.5 v. TG = 60.2 ± 6.7), progressive motility (%, CG = 26.9 ± 4.8 v. TG = 28.5 ± 4.8), percentage of rapid sperm (%, CG = 43.5 ± 8.8 v. TG = 45.7 ± 7.6), membrane integrity (%, CG = 20.1 ± 5.1 v. TG = 20.3 ± 6.3), and fertility (CG = 60% v. TG = 70%) between the groups. The results of this study showed that the use of cholesterol-loaded cyclodextrin did not affect sperm kinetic parameters and fertility in stallion with good quality in post-thaw semen. Further studies must be performed with stallions sensitive to freeze-thawing process.

Effects of Shao-Fu-Zhu-Yu-Tang on Motility of Human Sperm

2003 ◽  
Vol 31 (04) ◽  
pp. 573-579 ◽  
Author(s):  
Ching-Chiang Yang ◽  
Jung-Chou Chen ◽  
Guang-Wei Chen ◽  
Yi-Shuan Chen ◽  
J.G. Chung
Keyword(s):  
Chronic Prostatitis ◽  
Sperm Count ◽  
Semen Analysis ◽  
Human Sperm ◽  
Computer Assisted ◽  
Activity Levels ◽  
Human Semen ◽  
Before And After ◽  
Acrosin Activity

Shao-Fu-Zhu-Yu-Tang (SFZYT) is reportedly beneficial to sperm. In this study, we examined sperm acrosomal activity and serum free radical changes to evaluate the possible mechanism of SFZYT. A clinical study evaluated the sperm count and motility in 36 patients with chronic prostatitis before and after treatment for 60 days. The results revealed a significant increase in sperm motility after treatment as evaluated by computer-assisted semen analysis (17.27 ± 9.00 versus 28.29 ± 10.00, p < 0.01). An increase in sperm quantity and quality was observed by count and morphology with a high-powered intravital microscope. To gain an understanding of the mechanisms that caused this effect, we assessed sperm acrosin activity levels before (10.6 μ lu /106) and after medication (28.6 μ lu /106)( p < 0.01). The levels of the free radicals was relatively higher before medication, 2144, compared to a normal value of 780 after medication ( p < 0.01). In conclusion, SFZYT increased the motility and quality of human semen and this increase is related to an increase in sperm acrosin activity. SFZYT also works as a sperm antioxidant and antiaging agent.

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