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.	喬永峰, 李亞丹, 何寶明, 等. 精索靜脈曲張對不育患者精液質量的影響. 臨床醫學研究與實踐, 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, 凌曉輝, 等. 精索靜脈曲張不育患者氧化應激水平和精子 DNA 完整性及精液參數的相關性分析. 中華男科學雜志, 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.	史秋華, 李沙沙, 王磊. 精索靜脈高位結扎術聯合抗氧化劑治療對精索靜脈曲張不育癥患者精液質量的影響. 中國性科學, 2016, 25(5): 110-112.
9.	白廣煒, 韓大愚, 楊其運, 等. 大鼠精索靜脈曲張氧化應激介導附睪上皮緊密連接蛋白 ZO-1 損傷及對附睪功能的影響. 中華男科學雜志, 2019, 25(4): 302-308.
10.	夏煜琦, 程帆, 寧金卓, 等. GYY4137 對精索靜脈曲張大鼠附睪上皮細胞凋亡的影響. 中華實用診斷與治療雜志, 2019, 33(11): 1044-1048.
11.	寧金卓, 程帆, 余偉民, 等. GYY4137 對大鼠精索靜脈曲張生精功能損傷的保護作用. 中華實驗外科雜志, 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.	王新會, 張衛星, 王瑞, 等. 睪丸動脈及精索靜脈血流流速與精液質量的關系. 河南醫學研究, 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.	呼明闖, 章宏祥, 周發友, 等. 精索靜脈曲張的不育病人精子線粒體 DNA 片段缺失的調查. 蚌埠醫學院學報, 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.	梁丹陽, 戴漢川. PINK1/Parkin 通路在線粒體自噬氧化損傷中的作用. 中國細胞生物學學報, 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, 謝純平, 王君龍, 等. 精索靜脈曲張患者睪丸微循環變化與血清抑制素 B 及精液質量的關系. 實用醫學雜志, 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.	陳勇偉, 凌王濤, 王黎, 等. 一氧化氮、抑制素 B、胰島素樣因子 -3 與精索靜脈曲張病情程度相關性及表達意義. 中國臨床醫生雜志, 2021, 49(3): 324-327.
29.	康然, 秦松林, 王曉蘭. 精索靜脈曲張不育患者血清 8-OHdG、NO 及抑制素 B 水平變化及意義. 醫學理論與實踐, 2019, 32(18): 2945-2947.
30.	歐寧靜. 精子雄激素受體與精索靜脈曲張致生精功能受損的相關研究. 天津: 天津醫科大學, 2020.
31.	周海軍, 王永傳, 王曉宇, 等. 精索靜脈曲張對大鼠前列腺雄激素受體及睪酮水平影響的實驗研究. 中國男科學雜志, 2019, 33(5): 6-9.
32.	陳云斌. 精索靜脈曲張與雄性激素水平的相關性研究. 南寧: 廣西醫科大學, 2013.
33.	張芳, 徐菁. 環磷酸腺苷反應元件調控因子在精索靜脈曲張大鼠睪丸的表達及意義. 中國藥物與臨床, 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, 余偉民, 饒婷, 等. 精索靜脈曲張大鼠睪丸細胞自噬的初步研究. 現代泌尿外科雜志, 2017, 22(5): 381-386.
36.	吳承, 朱少明, 程帆, 等. 精索靜脈曲張大鼠睪丸自噬對生精細胞的影響. 中華男科學雜志, 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.	杜漢承, 林文東, 丁小明. 茶多酚對精索靜脈曲張大鼠生精細胞凋亡的影響及機制研究. 局解手術學雜志, 2021, 30(3): 185-189.
39.	阮衍泰, 郜亮, 徐貴江, 等. 精索靜脈曲張對孕前男性精漿生化及精子 DNA 完整性的影響. 中國男科學雜志, 2021, 35(2): 54-56, 60.
40.	張燚, 李環. DBP 介導 Cx43 對大鼠睪丸 Leydig 細胞睪酮合成的影響. 北華大學學報 (自然科學版), 2015, 16(2): 191-194.
41.	劉國霖, 張澤敏, 唐圓圓, 等. 大鼠精索靜脈曲張對睪丸生精細胞 Cx43 表達的影響. 北華大學學報(自然科學版), 2016, 17(5): 624-627.
42.	賀情情, 劉小彭, 范年豐, 等. 大鼠精索靜脈曲張睪丸組織的蛋白質組學研究. 中華腔鏡泌尿外科雜志(電子版), 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, 翟艷慧, 呂昌敏, 等. CatSper1 在精索靜脈曲張模型大鼠精子中的差異表達及左卡尼汀對其的保護作用. 中華男科學雜志, 2019, 25(11): 978-983.
45.	潘建剛, 朱志榮, 鈕莉莉, 等. 單側精索靜脈曲張模型大鼠雙側睪丸 Claudin-11 表達及血-睪屏障變化的實驗研究. 中華男科學雜志, 2019, 25(1): 77-81.
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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. 喬永峰, 李亞丹, 何寶明, 等. 精索靜脈曲張對不育患者精液質量的影響. 臨床醫學研究與實踐, 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, 凌曉輝, 等. 精索靜脈曲張不育患者氧化應激水平和精子 DNA 完整性及精液參數的相關性分析. 中華男科學雜志, 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. 史秋華, 李沙沙, 王磊. 精索靜脈高位結扎術聯合抗氧化劑治療對精索靜脈曲張不育癥患者精液質量的影響. 中國性科學, 2016, 25(5): 110-112.
9. 白廣煒, 韓大愚, 楊其運, 等. 大鼠精索靜脈曲張氧化應激介導附睪上皮緊密連接蛋白 ZO-1 損傷及對附睪功能的影響. 中華男科學雜志, 2019, 25(4): 302-308.
10. 夏煜琦, 程帆, 寧金卓, 等. GYY4137 對精索靜脈曲張大鼠附睪上皮細胞凋亡的影響. 中華實用診斷與治療雜志, 2019, 33(11): 1044-1048.
11. 寧金卓, 程帆, 余偉民, 等. GYY4137 對大鼠精索靜脈曲張生精功能損傷的保護作用. 中華實驗外科雜志, 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. 王新會, 張衛星, 王瑞, 等. 睪丸動脈及精索靜脈血流流速與精液質量的關系. 河南醫學研究, 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. 呼明闖, 章宏祥, 周發友, 等. 精索靜脈曲張的不育病人精子線粒體 DNA 片段缺失的調查. 蚌埠醫學院學報, 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. 梁丹陽, 戴漢川. PINK1/Parkin 通路在線粒體自噬氧化損傷中的作用. 中國細胞生物學學報, 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, 謝純平, 王君龍, 等. 精索靜脈曲張患者睪丸微循環變化與血清抑制素 B 及精液質量的關系. 實用醫學雜志, 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. 陳勇偉, 凌王濤, 王黎, 等. 一氧化氮、抑制素 B、胰島素樣因子 -3 與精索靜脈曲張病情程度相關性及表達意義. 中國臨床醫生雜志, 2021, 49(3): 324-327.
29. 康然, 秦松林, 王曉蘭. 精索靜脈曲張不育患者血清 8-OHdG、NO 及抑制素 B 水平變化及意義. 醫學理論與實踐, 2019, 32(18): 2945-2947.
30. 歐寧靜. 精子雄激素受體與精索靜脈曲張致生精功能受損的相關研究. 天津: 天津醫科大學, 2020.
31. 周海軍, 王永傳, 王曉宇, 等. 精索靜脈曲張對大鼠前列腺雄激素受體及睪酮水平影響的實驗研究. 中國男科學雜志, 2019, 33(5): 6-9.
32. 陳云斌. 精索靜脈曲張與雄性激素水平的相關性研究. 南寧: 廣西醫科大學, 2013.
33. 張芳, 徐菁. 環磷酸腺苷反應元件調控因子在精索靜脈曲張大鼠睪丸的表達及意義. 中國藥物與臨床, 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, 余偉民, 饒婷, 等. 精索靜脈曲張大鼠睪丸細胞自噬的初步研究. 現代泌尿外科雜志, 2017, 22(5): 381-386.
36. 吳承, 朱少明, 程帆, 等. 精索靜脈曲張大鼠睪丸自噬對生精細胞的影響. 中華男科學雜志, 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. 杜漢承, 林文東, 丁小明. 茶多酚對精索靜脈曲張大鼠生精細胞凋亡的影響及機制研究. 局解手術學雜志, 2021, 30(3): 185-189.
39. 阮衍泰, 郜亮, 徐貴江, 等. 精索靜脈曲張對孕前男性精漿生化及精子 DNA 完整性的影響. 中國男科學雜志, 2021, 35(2): 54-56, 60.
40. 張燚, 李環. DBP 介導 Cx43 對大鼠睪丸 Leydig 細胞睪酮合成的影響. 北華大學學報 (自然科學版), 2015, 16(2): 191-194.
41. 劉國霖, 張澤敏, 唐圓圓, 等. 大鼠精索靜脈曲張對睪丸生精細胞 Cx43 表達的影響. 北華大學學報(自然科學版), 2016, 17(5): 624-627.
42. 賀情情, 劉小彭, 范年豐, 等. 大鼠精索靜脈曲張睪丸組織的蛋白質組學研究. 中華腔鏡泌尿外科雜志(電子版), 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, 翟艷慧, 呂昌敏, 等. CatSper1 在精索靜脈曲張模型大鼠精子中的差異表達及左卡尼汀對其的保護作用. 中華男科學雜志, 2019, 25(11): 978-983.
45. 潘建剛, 朱志榮, 鈕莉莉, 等. 單側精索靜脈曲張模型大鼠雙側睪丸 Claudin-11 表達及血-睪屏障變化的實驗研究. 中華男科學雜志, 2019, 25(1): 77-81.
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