Advance of varicocele on testicular spermatogenesis_West China Medical Journal

Authors：

WANG Puze ¹ , CAO Dehong ¹ , CHEN Zeyu ¹ , LI Jin ¹ , HUANG Yin ¹ , WANG Ruyi ^1,2 , CHEN Bo ¹ , ZHU Yuchun ¹ ,  WEI Qiang ¹ , DONG Qiang ¹ ,  LIU Liangren ¹

1. Department of Urology, West China Hospital / Institute of Urology, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Urology, Hospital of Chengdu University, Chengdu, Sichuan 610081, P. R. China;

Corresponding author：

WEI Qiang, Email: weiqiang933@126.com; LIU Liangren, Email: liuliangren5-17@163.com

Keywords：

Varicocele; spermatogenesis; abnormal semen; molecular mechanism

DOI：

10.7507/1002-0179.202111010

Video：

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Abstract Full text Figures/Tables Video References Cited by

Varicocele (VC) is one of the common diseases of the male genitourinary system, and its incidence is higher in young adults. Among them, 80%-98% of VC are more likely to occur in the left spermatic vein. Previous research has found that VC could affect the temperature of the local microenvironment of the testis, oxidative stress process in the spermatogenic environment, mitochondrial function of sperm, endocrine system, and apoptosis of testes and epididymal cells. Therefore, VC will have an important impact on spermatogenic process of the testicles to cause male infertility. However, the specific molecular mechanism of VC affecting male spermatogenesis has not been fully studied. Therefore, this article will review the effect and mechanism of VC on testicular spermatogenesis.

Citation： WANG Puze, CAO Dehong, CHEN Zeyu, LI Jin, HUANG Yin, WANG Ruyi, CHEN Bo, ZHU Yuchun, WEI Qiang, DONG Qiang, LIU Liangren. Advance of varicocele on testicular spermatogenesis. West China Medical Journal, 2023, 38(2): 311-315. doi: 10.7507/1002-0179.202111010 Copy

1.	Reesink DJ, Huisman PM, Wiltink J, et al. Sneeze and pop: a ruptured varicocele; analysis of literature, guided by a well-documented case-report. BMC Urol, 2019, 19(1): 14.
2.	Jungwirth A, Diemer T, Kopa Z, et al. EAU guidelines on male infertility. (2018-03)[2021-11-01]. https://d56bochluxqnz.cloudfront.net/media/EAU-Guidelines-on-Male-Infertility-2018-large-text.pdf.
3.	乔永峰, 李亚丹, 何宝明, 等. 精索静脉曲张对不育患者精液质量的影响. 临床医学研究与实践, 2019, 4(23): 124-125, 131.
4.	Cho CL, Esteves SC, Agarwal A. Novel insights into the pathophysiology of varicocele and its association with reactive oxygen species and sperm DNA fragmentation. Asian J Androl, 2016, 18(2): 186-193.
5.	Khosravanian H, Razi M, Farokhi F, et al. Simultaneous administration of dexamethasone and vitamin E reversed experimental varicocele-induced impact in testicular tissue in rats; correlation with hsp70-2 chaperone expression. Int Braz J Urol, 2015, 41(4): 773-790.
6.	符浩, 宋汶珂, 凌晓辉, 等. 精索静脉曲张不育患者氧化应激水平和精子 DNA 完整性及精液参数的相关性分析. 中华男科学杂志, 2016, 22(6): 530-533.
7.	Bhanmeechao C, Srisuwatanasagul S, Prapaiwan N, et al. Reproductive aging in male dogs: the epididymal sperm defects and expression of androgen receptor in reproductive tissues. Theriogenology, 2018, 108: 74-80.
8.	史秋华, 李沙沙, 王磊. 精索静脉高位结扎术联合抗氧化剂治疗对精索静脉曲张不育症患者精液质量的影响. 中国性科学, 2016, 25(5): 110-112.
9.	白广炜, 韩大愚, 杨其运, 等. 大鼠精索静脉曲张氧化应激介导附睾上皮紧密连接蛋白 ZO-1 损伤及对附睾功能的影响. 中华男科学杂志, 2019, 25(4): 302-308.
10.	夏煜琦, 程帆, 宁金卓, 等. GYY4137 对精索静脉曲张大鼠附睾上皮细胞凋亡的影响. 中华实用诊断与治疗杂志, 2019, 33(11): 1044-1048.
11.	宁金卓, 程帆, 余伟民, 等. GYY4137 对大鼠精索静脉曲张生精功能损伤的保护作用. 中华实验外科杂志, 2020, 37(8): 1457-1460.
12.	Goldstein M, Eid JF. Elevation of intratesticular and scrotal skin surface temperature in men with varicocele. J Urol, 1989, 142(3): 743-745.
13.	Paick S, Choi WS. Varicocele and testicular pain: a review. World J Mens Health, 2019, 37(1): 4-11.
14.	王新会, 张卫星, 王瑞, 等. 睾丸动脉及精索静脉血流流速与精液质量的关系. 河南医学研究, 2017, 26(4): 591-593.
15.	Jin G, Liu J, Qin Q, et al. Increased level of c-kit in semen of infertile patients with varicocele. Urol J, 2017, 14(2): 3023-3027.
16.	Zhang G, Wang Z, Ling X, et al. Mitochondrial biomarkers reflect semen quality: results from the MARCHS study in Chongqing, China. PLoS One, 2016, 11(12): e0168823.
17.	Malik AN, Czajka A. Is mitochondrial DNA content a potential biomarker of mitochondrial dysfunction?. Mitochondrion. 2013, 13(5): 481-492.
18.	Tavalaee M, Bahreinian M, Barekat F, et al. Effect of varicocelectomy on sperm functional characteristics and DNA methylation. Andrologia, 2015, 47(8): 904-909.
19.	Santana VP, James ER, Miranda-Furtado CL, et al. Differential DNA methylation pattern and sperm quality in men with varicocele. Fertil Steril, 2020, 114(4): 770-778.
20.	呼明闯, 章宏祥, 周发友, 等. 精索静脉曲张的不育病人精子线粒体 DNA 片段缺失的调查. 蚌埠医学院学报, 2020, 45(6): 809-811.
21.	Agarwal A, Sharma R, Samanta L, et al. Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility. Asian J Androl, 2016, 18(2): 282-291.
22.	Agarwal A, Sharma R, Durairajanayagam D, et al. Differential proteomic profiling of spermatozoal proteins of infertile men with unilateral or bilateral varicocele. Urology, 2015, 85(3): 580-588.
23.	Eid N, Ito Y, Horibe A, et al. A method for in vivo induction and ultrastructural detection of mitophagy in sertoli cells. Methods Mol Biol, 2018, 1748: 103-112.
24.	梁丹阳, 戴汉川. PINK1/Parkin 通路在线粒体自噬氧化损伤中的作用. 中国细胞生物学学报, 2018, 40(1): 116-123.
25.	Zhu SM, Rao T, Yang X, et al. Autophagy may play an important role in varicocele. Mol Med Rep, 2017, 16(4): 5471-5479.
26.	廖森成, 谢纯平, 王君龙, 等. 精索静脉曲张患者睾丸微循环变化与血清抑制素 B 及精液质量的关系. 实用医学杂志, 2016, 32(11): 1844-1846.
27.	Damsgaard J, Joensen UN, Carlsen E, et al. Varicocele is associated with impaired semen quality and reproductive hormone levels: a study of 7035 healthy young men from six European countries. Eur Urol, 2016, 70(6): 1019-1029.
28.	陈勇伟, 凌王涛, 王黎, 等. 一氧化氮、抑制素 B、胰岛素样因子 -3 与精索静脉曲张病情程度相关性及表达意义. 中国临床医生杂志, 2021, 49(3): 324-327.
29.	康然, 秦松林, 王晓兰. 精索静脉曲张不育患者血清 8-OHdG、NO 及抑制素 B 水平变化及意义. 医学理论与实践, 2019, 32(18): 2945-2947.
30.	欧宁静. 精子雄激素受体与精索静脉曲张致生精功能受损的相关研究. 天津: 天津医科大学, 2020.
31.	周海军, 王永传, 王晓宇, 等. 精索静脉曲张对大鼠前列腺雄激素受体及睾酮水平影响的实验研究. 中国男科学杂志, 2019, 33(5): 6-9.
32.	陈云斌. 精索静脉曲张与雄性激素水平的相关性研究. 南宁: 广西医科大学, 2013.
33.	张芳, 徐菁. 环磷酸腺苷反应元件调控因子在精索静脉曲张大鼠睾丸的表达及意义. 中国药物与临床, 2017, 17(4): 506-508.
34.	Gandhi J, Dagur G, Sheynkin YR, et al. Testicular compartment syndrome: an overview of pathophysiology, etiology, evaluation, and management. Transl Androl Urol, 2016, 5(6): 927-934.
35.	朱少明, 余伟民, 饶婷, 等. 精索静脉曲张大鼠睾丸细胞自噬的初步研究. 现代泌尿外科杂志, 2017, 22(5): 381-386.
36.	吴承, 朱少明, 程帆, 等. 精索静脉曲张大鼠睾丸自噬对生精细胞的影响. 中华男科学杂志, 2020, 26(2): 111-117.
37.	Vaz ADC, Paccola CC, Mendes TB, et al. Sertoli cell alterations in peripubertal varicocelized rats: evidence of primary damage on spermatogenesis. J Histochem Cytochem, 2020, 68(3): 185-198.
38.	杜汉承, 林文东, 丁小明. 茶多酚对精索静脉曲张大鼠生精细胞凋亡的影响及机制研究. 局解手术学杂志, 2021, 30(3): 185-189.
39.	阮衍泰, 郜亮, 徐贵江, 等. 精索静脉曲张对孕前男性精浆生化及精子 DNA 完整性的影响. 中国男科学杂志, 2021, 35(2): 54-56, 60.
40.	张燚, 李环. DBP 介导 Cx43 对大鼠睾丸 Leydig 细胞睾酮合成的影响. 北华大学学报 (自然科学版), 2015, 16(2): 191-194.
41.	刘国霖, 张泽敏, 唐圆圆, 等. 大鼠精索静脉曲张对睾丸生精细胞 Cx43 表达的影响. 北华大学学报(自然科学版), 2016, 17(5): 624-627.
42.	贺情情, 刘小彭, 范年丰, 等. 大鼠精索静脉曲张睾丸组织的蛋白质组学研究. 中华腔镜泌尿外科杂志(电子版), 2014, 8(2): 135-139.
43.	Yang B, Yang Y, Liu Y, et al. Molecular characteristics of varicocele: integration of whole-exome and transcriptome sequencing. Fertil Steril, 2021, 115(2): 363-372.
44.	王世平, 翟艳慧, 吕昌敏, 等. CatSper1 在精索静脉曲张模型大鼠精子中的差异表达及左卡尼汀对其的保护作用. 中华男科学杂志, 2019, 25(11): 978-983.
45.	潘建刚, 朱志荣, 钮莉莉, 等. 单侧精索静脉曲张模型大鼠双侧睾丸 Claudin-11 表达及血-睾屏障变化的实验研究. 中华男科学杂志, 2019, 25(1): 77-81.
46.	Zhang L, Zhao X, Wang F, et al. Effects of Morinda officinalis polysaccharide on experimental varicocele rats. Evid Based Complement Alternat Med, 2016: 5365291.
47.	张丽虹, 王锋, 赵小贞, 等. MicroRNA-181d-5p 通过 PTEN 参与睾丸支持细胞间紧密连接损伤. 解剖学杂志, 2021, 44(2): 95-100.
48.	Santana VP, Miranda-Furtado CL, de Oliveira-Gennaro FG, et al. Genetics and epigenetics of varicocele pathophysiology: an overview. J Assist Reprod Genet, 2017, 34(7): 839-847.
49.	Santana VP, Miranda-Furtado CL, Pedroso DCC, et al. The relationship among sperm global DNA methylation, telomere length, and DNA fragmentation in varicocele: a cross-sectional study of 20 cases. Syst Biol Reprod Med, 2019, 65(2): 95-104.

1. Reesink DJ, Huisman PM, Wiltink J, et al. Sneeze and pop: a ruptured varicocele; analysis of literature, guided by a well-documented case-report. BMC Urol, 2019, 19(1): 14.
2. Jungwirth A, Diemer T, Kopa Z, et al. EAU guidelines on male infertility. (2018-03)[2021-11-01]. https://d56bochluxqnz.cloudfront.net/media/EAU-Guidelines-on-Male-Infertility-2018-large-text.pdf.
3. 乔永峰, 李亚丹, 何宝明, 等. 精索静脉曲张对不育患者精液质量的影响. 临床医学研究与实践, 2019, 4(23): 124-125, 131.
4. Cho CL, Esteves SC, Agarwal A. Novel insights into the pathophysiology of varicocele and its association with reactive oxygen species and sperm DNA fragmentation. Asian J Androl, 2016, 18(2): 186-193.
5. Khosravanian H, Razi M, Farokhi F, et al. Simultaneous administration of dexamethasone and vitamin E reversed experimental varicocele-induced impact in testicular tissue in rats; correlation with hsp70-2 chaperone expression. Int Braz J Urol, 2015, 41(4): 773-790.
6. 符浩, 宋汶珂, 凌晓辉, 等. 精索静脉曲张不育患者氧化应激水平和精子 DNA 完整性及精液参数的相关性分析. 中华男科学杂志, 2016, 22(6): 530-533.
7. Bhanmeechao C, Srisuwatanasagul S, Prapaiwan N, et al. Reproductive aging in male dogs: the epididymal sperm defects and expression of androgen receptor in reproductive tissues. Theriogenology, 2018, 108: 74-80.
8. 史秋华, 李沙沙, 王磊. 精索静脉高位结扎术联合抗氧化剂治疗对精索静脉曲张不育症患者精液质量的影响. 中国性科学, 2016, 25(5): 110-112.
9. 白广炜, 韩大愚, 杨其运, 等. 大鼠精索静脉曲张氧化应激介导附睾上皮紧密连接蛋白 ZO-1 损伤及对附睾功能的影响. 中华男科学杂志, 2019, 25(4): 302-308.
10. 夏煜琦, 程帆, 宁金卓, 等. GYY4137 对精索静脉曲张大鼠附睾上皮细胞凋亡的影响. 中华实用诊断与治疗杂志, 2019, 33(11): 1044-1048.
11. 宁金卓, 程帆, 余伟民, 等. GYY4137 对大鼠精索静脉曲张生精功能损伤的保护作用. 中华实验外科杂志, 2020, 37(8): 1457-1460.
12. Goldstein M, Eid JF. Elevation of intratesticular and scrotal skin surface temperature in men with varicocele. J Urol, 1989, 142(3): 743-745.
13. Paick S, Choi WS. Varicocele and testicular pain: a review. World J Mens Health, 2019, 37(1): 4-11.
14. 王新会, 张卫星, 王瑞, 等. 睾丸动脉及精索静脉血流流速与精液质量的关系. 河南医学研究, 2017, 26(4): 591-593.
15. Jin G, Liu J, Qin Q, et al. Increased level of c-kit in semen of infertile patients with varicocele. Urol J, 2017, 14(2): 3023-3027.
16. Zhang G, Wang Z, Ling X, et al. Mitochondrial biomarkers reflect semen quality: results from the MARCHS study in Chongqing, China. PLoS One, 2016, 11(12): e0168823.
17. Malik AN, Czajka A. Is mitochondrial DNA content a potential biomarker of mitochondrial dysfunction?. Mitochondrion. 2013, 13(5): 481-492.
18. Tavalaee M, Bahreinian M, Barekat F, et al. Effect of varicocelectomy on sperm functional characteristics and DNA methylation. Andrologia, 2015, 47(8): 904-909.
19. Santana VP, James ER, Miranda-Furtado CL, et al. Differential DNA methylation pattern and sperm quality in men with varicocele. Fertil Steril, 2020, 114(4): 770-778.
20. 呼明闯, 章宏祥, 周发友, 等. 精索静脉曲张的不育病人精子线粒体 DNA 片段缺失的调查. 蚌埠医学院学报, 2020, 45(6): 809-811.
21. Agarwal A, Sharma R, Samanta L, et al. Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility. Asian J Androl, 2016, 18(2): 282-291.
22. Agarwal A, Sharma R, Durairajanayagam D, et al. Differential proteomic profiling of spermatozoal proteins of infertile men with unilateral or bilateral varicocele. Urology, 2015, 85(3): 580-588.
23. Eid N, Ito Y, Horibe A, et al. A method for in vivo induction and ultrastructural detection of mitophagy in sertoli cells. Methods Mol Biol, 2018, 1748: 103-112.
24. 梁丹阳, 戴汉川. PINK1/Parkin 通路在线粒体自噬氧化损伤中的作用. 中国细胞生物学学报, 2018, 40(1): 116-123.
25. Zhu SM, Rao T, Yang X, et al. Autophagy may play an important role in varicocele. Mol Med Rep, 2017, 16(4): 5471-5479.
26. 廖森成, 谢纯平, 王君龙, 等. 精索静脉曲张患者睾丸微循环变化与血清抑制素 B 及精液质量的关系. 实用医学杂志, 2016, 32(11): 1844-1846.
27. Damsgaard J, Joensen UN, Carlsen E, et al. Varicocele is associated with impaired semen quality and reproductive hormone levels: a study of 7035 healthy young men from six European countries. Eur Urol, 2016, 70(6): 1019-1029.
28. 陈勇伟, 凌王涛, 王黎, 等. 一氧化氮、抑制素 B、胰岛素样因子 -3 与精索静脉曲张病情程度相关性及表达意义. 中国临床医生杂志, 2021, 49(3): 324-327.
29. 康然, 秦松林, 王晓兰. 精索静脉曲张不育患者血清 8-OHdG、NO 及抑制素 B 水平变化及意义. 医学理论与实践, 2019, 32(18): 2945-2947.
30. 欧宁静. 精子雄激素受体与精索静脉曲张致生精功能受损的相关研究. 天津: 天津医科大学, 2020.
31. 周海军, 王永传, 王晓宇, 等. 精索静脉曲张对大鼠前列腺雄激素受体及睾酮水平影响的实验研究. 中国男科学杂志, 2019, 33(5): 6-9.
32. 陈云斌. 精索静脉曲张与雄性激素水平的相关性研究. 南宁: 广西医科大学, 2013.
33. 张芳, 徐菁. 环磷酸腺苷反应元件调控因子在精索静脉曲张大鼠睾丸的表达及意义. 中国药物与临床, 2017, 17(4): 506-508.
34. Gandhi J, Dagur G, Sheynkin YR, et al. Testicular compartment syndrome: an overview of pathophysiology, etiology, evaluation, and management. Transl Androl Urol, 2016, 5(6): 927-934.
35. 朱少明, 余伟民, 饶婷, 等. 精索静脉曲张大鼠睾丸细胞自噬的初步研究. 现代泌尿外科杂志, 2017, 22(5): 381-386.
36. 吴承, 朱少明, 程帆, 等. 精索静脉曲张大鼠睾丸自噬对生精细胞的影响. 中华男科学杂志, 2020, 26(2): 111-117.
37. Vaz ADC, Paccola CC, Mendes TB, et al. Sertoli cell alterations in peripubertal varicocelized rats: evidence of primary damage on spermatogenesis. J Histochem Cytochem, 2020, 68(3): 185-198.
38. 杜汉承, 林文东, 丁小明. 茶多酚对精索静脉曲张大鼠生精细胞凋亡的影响及机制研究. 局解手术学杂志, 2021, 30(3): 185-189.
39. 阮衍泰, 郜亮, 徐贵江, 等. 精索静脉曲张对孕前男性精浆生化及精子 DNA 完整性的影响. 中国男科学杂志, 2021, 35(2): 54-56, 60.
40. 张燚, 李环. DBP 介导 Cx43 对大鼠睾丸 Leydig 细胞睾酮合成的影响. 北华大学学报 (自然科学版), 2015, 16(2): 191-194.
41. 刘国霖, 张泽敏, 唐圆圆, 等. 大鼠精索静脉曲张对睾丸生精细胞 Cx43 表达的影响. 北华大学学报(自然科学版), 2016, 17(5): 624-627.
42. 贺情情, 刘小彭, 范年丰, 等. 大鼠精索静脉曲张睾丸组织的蛋白质组学研究. 中华腔镜泌尿外科杂志(电子版), 2014, 8(2): 135-139.
43. Yang B, Yang Y, Liu Y, et al. Molecular characteristics of varicocele: integration of whole-exome and transcriptome sequencing. Fertil Steril, 2021, 115(2): 363-372.
44. 王世平, 翟艳慧, 吕昌敏, 等. CatSper1 在精索静脉曲张模型大鼠精子中的差异表达及左卡尼汀对其的保护作用. 中华男科学杂志, 2019, 25(11): 978-983.
45. 潘建刚, 朱志荣, 钮莉莉, 等. 单侧精索静脉曲张模型大鼠双侧睾丸 Claudin-11 表达及血-睾屏障变化的实验研究. 中华男科学杂志, 2019, 25(1): 77-81.
46. Zhang L, Zhao X, Wang F, et al. Effects of Morinda officinalis polysaccharide on experimental varicocele rats. Evid Based Complement Alternat Med, 2016: 5365291.
47. 张丽虹, 王锋, 赵小贞, 等. MicroRNA-181d-5p 通过 PTEN 参与睾丸支持细胞间紧密连接损伤. 解剖学杂志, 2021, 44(2): 95-100.
48. Santana VP, Miranda-Furtado CL, de Oliveira-Gennaro FG, et al. Genetics and epigenetics of varicocele pathophysiology: an overview. J Assist Reprod Genet, 2017, 34(7): 839-847.
49. Santana VP, Miranda-Furtado CL, Pedroso DCC, et al. The relationship among sperm global DNA methylation, telomere length, and DNA fragmentation in varicocele: a cross-sectional study of 20 cases. Syst Biol Reprod Med, 2019, 65(2): 95-104.

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