Table of Contents  
LETTER TO THE EDITOR
Year : 2015  |  Volume : 17  |  Issue : 5  |  Page : 859-860

Glutathione S-transferase T1: a potential marker for the selection of varicocelectomy in infertile male patients with varicocele


1 Department of Surgery, First Affiliated Hospital, School of Medicine, Xi'an Jiao Tong University, Xi'an 710061, China
2 Department of Urology, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China

Date of Submission15-Sep-2014
Date of Decision15-Oct-2014
Date of Acceptance26-Dec-2014
Date of Web Publication06-Feb-2015

Correspondence Address:
Jun-Ping Xing
Department of Surgery, First Affiliated Hospital, School of Medicine, Xi'an Jiao Tong University, Xi'an 710061
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1008-682X.149179

Rights and Permissions

How to cite this article:
Wu QF, Tang KF, Sun JH, Xing JP. Glutathione S-transferase T1: a potential marker for the selection of varicocelectomy in infertile male patients with varicocele. Asian J Androl 2015;17:859-60

How to cite this URL:
Wu QF, Tang KF, Sun JH, Xing JP. Glutathione S-transferase T1: a potential marker for the selection of varicocelectomy in infertile male patients with varicocele. Asian J Androl [serial online] 2015 [cited 2020 Sep 21];17:859-60. Available from: http://www.ajandrology.com/text.asp?2015/17/5/859/149179 - DOI: 10.4103/1008-682X.149179

Dear Editor,

Varicocele is a common cause of male infertility, and the prevalence of varicocele among men attending infertility clinics ranges from 30% to 40%. The effects of varicocele are diverse, but often result in semen abnormalities, decreased testicular volume and decline in Leydig cell function.

Although varicocele can cause serious complications, its surgical treatment is quite simple. Previous studies have shown that varicocelectomy is an effective treatment for varicocele and can result in an improvement in semen parameters as well as the natural pregnancy rates of infertile couples. [1] These findings suggest that varicocelectomy improves sperm variables and fertility rates. Therefore, varicocelectomy is widely used for the treatment of infertile men with varicocele. To improve the therapeutic effect of varicocelectomy, it is performed in patients with subclinical varicocele. [2] Varicocelectomy is also performed in adolescents to prevent the development of male infertility due to varicocele, and this procedure may be more effective in adolescents than in adults. [3] However, there is a significant risk of excessive usage of varicocelectomy.

Contemporary research suggests that varicocelectomy may have limited therapeutic efficiency. Some studies have shown that men undergoing varicocelectomy exhibit only a slight improvement in postoperative semen parameters, and the procedure might not result in an increase in pregnancy rate. [4]

These study results suggest that while varicocelectomy is an effective therapy for varicocele, it might not be suitable for all patients. Moreover, the risk of excessive usage of varicocelectomy is a concern. Therefore, clinicians face the tough problem of identifying suitable candidates for varicocelectomy and preventing its excessive usage.

To preselect patients who would benefit the most, it is important to define factors predictive of a positive response to varicocelectomy in infertile men. Several studies have suggested that oxidative stress mainly caused by reactive oxygen species (ROS) is involved in the pathogenesis of varicocele. [5],[6] Glutathione S-transferases (GSTs) - an important superfamily of phase 2 drug-metabolizing enzymes generated in response to oxidative stress - play an important role in cell protection by performing functions like catalyzing the conjugation of a large variety of endogenous and exogenous compounds including ROS, carcinogenic compounds, and their metabolites. A previous study clearly demonstrated an abundance of GSTs in the male reproductive tract and showed that GSTs play important roles in the protection of sperm against oxidative stress. [7] Genes encoding human cytosolic GSTs exhibit genetic polymorphism, and homozygous deletions in these genes result in null genotypes. Many genetic polymorphisms lead to altered activities of GSTs, which may be partially responsible for an individual's susceptibility to oxidative damage. GSTT1, a member of the GST gene family, is polymorphic in the human population. Our previous study has shown a possible relationship between the GSTT1 null genotype and the susceptibility to male infertility in patients with varicocele, and we found that the GSTT1 positive genotype improved the antioxidant capacity, reduced the levels of ROS in seminal plasma, and prevented injury caused by ROS to the sperm DNA in infertile patients with varicocele. [8] A Japanese group has reported that after varicocelectomy, the GSTT1 positive genotype is associated with an improvement in the seminal findings of infertile patients with varicocele. [9] In recent clinical practice, we have also found that patients with the GSTT1 positive genotype have better responses to varicocelectomy than do patients with the GSTT1 null genotype (data not shown). Based on the findings of these studies, we propose that a GSTT1 positive genotype is a potential marker for the selection of varicocelectomy in infertile male patients with varicocele.

Accordingly, we propose that only infertile male patients with the GSTT1 positive genotype should be selected to undergo varicocelectomy; patients with the GSTT1 null genotype need not undergo varicocelectomy because of their negative responses to this surgery. If this proposal is approved, we must reevaluate the necessity of treatment of varicocele in adolescents with the GSTT1 positive genotype because these adolescents might not develop male infertility in the future. We think that varicocelectomy should be performed in the population with the GSTT1 positive genotype, especially the adolescent population, only when changes in sperm function or structure are detected. This will lower the risk of excessive usage and improve the therapeutic effect of varicocelectomy. Apart from the GSTT1 polymorphisms, there are some gene polymorphisms in other phase 2 drug-metabolizing enzymes that have shown potential as markers for the selection of infertile male patients with varicocele to undergo varicocelectomy. [9],[10] However, more prospective cohort studies and large-scale randomized trials are needed to further evaluate all these potential markers.

In addition, the causes of male infertility are complex, only a small fraction of cases of male infertility is related to varicocele. Reduced male fertility can be caused by congenital and acquired urogenital abnormalities, infections of the male accessory glands, endocrine disturbances, genetic abnormalities, and immunological factors. Therefore, to lower the risk of excessive usage of varicocelectomy, we still need to evaluate the infertile male patients carefully to rule out other possible reasons for infertility before performing varicocelectomy.


  Author Contributions Top


JHS conceived and created the framework for the letter, collected the data, and drafted the manuscript. KFT conceived and created the framework for the letter, collected the data, and drafted the manuscript. QFW conceived and created the framework for the letter, evaluated the data, drafted the manuscript, and edited the manuscript. JPX conceived and created the framework for the letter, evaluated the data, and edited the manuscript. All authors have read and approved the final manuscript.


  Competing Interests Top


All authors declare no competing interests.


  Acknowledgments Top


This work was supported by the National Natural Science Foundation of China (No. 81300541).

 
  References Top

1.
Baker K, McGill J, Sharma R, Agarwal A, Sabanegh E Jr. Pregnancy after varicocelectomy: impact of postoperative motility and DFI. Urology 2013; 81: 760-6.  Back to cited text no. 1
    
2.
Seo JT, Kim KT, Moon MH, Kim WT. The significance of microsurgical varicocelectomy in the treatment of subclinical varicocele. Fertil Steril 2010; 93: 1907-10.  Back to cited text no. 2
    
3.
Lacerda JI, Del Giudice PT, da Silva BF, Nichi M, Fariello RM, et al. Adolescent varicocele: improved sperm function after varicocelectomy. Fertil Steril 2011; 95: 994-9.  Back to cited text no. 3
    
4.
Evers JL, Collins JA. Assessment of efficacy of varicocele repair for male subfertility: a systematic review. Lancet 2003; 361: 1849-52.  Back to cited text no. 4
    
5.
Romeo C, Ientile R, Impellizzeri P, Turiaco N, Teletta M, et al. Preliminary report on nitric oxide-mediated oxidative damage in adolescent varicocele. Hum Reprod 2003; 18: 26-9.  Back to cited text no. 5
    
6.
Mostafa T, Anis TH, Ghazi S, El-Nashar AR, Imam H, et al. Reactive oxygen species and antioxidants relationship in the internal spermatic vein blood of infertile men with varicocele. Asian J Androl 2006; 8: 451-4.  Back to cited text no. 6
    
7.
Rao AV, Shaha C. Role of glutathione S-transferases in oxidative stress-induced male germ cell apoptosis. Free Radic Biol Med 2000; 29: 1015-27.  Back to cited text no. 7
    
8.
Wu Q, Xing J, Xue W, Sun J, Wang X, et al. Influence of polymorphism of glutathione S-transferase T1 on Chinese infertile patients with varicocele. Fertil Steril 2009; 91: 960-2.  Back to cited text no. 8
    
9.
Okubo K, Nagahama K, Kamoto T, Okuno H, Ogawa O, et al. GSTT1 and GSTM1 polymorphisms are associated with improvement in seminal findings after varicocelectomy. Fertil Steril 2005; 83: 1579-80.  Back to cited text no. 9
    
10.
Ichioka K, Nagahama K, Okubo K, Soda T, Ogawa O, et al. Genetic polymorphisms in glutathione S-transferase T1 affect the surgical outcome of varicocelectomies in infertile patients. Asian J Androl 2009; 11: 333-41.  Back to cited text no. 10
    




 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Author Contributions
Competing Interests
Acknowledgments
References

 Article Access Statistics
    Viewed1765    
    Printed44    
    Emailed0    
    PDF Downloaded255    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]