严重生精障碍患者精子DNA碎片指数与血清Hcy水平的相关性研究
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摘要
目的探讨严重生精障碍患者精子DNA碎片指数与血清Hcy水平的相关性研究。方法 2015年12月~2017年2月期间就诊的严重生精障碍男性患者56例,按WHO标准分为严重无、少精子症组25例和弱精子症组31例,对照组为无生育障碍的男性27例。对所有纳入研究者运用全自动精液分析仪进行精子参数分析,精子DNA碎片指数和血清Hcy水平的检测分别运用精子染色质扩散法和酶比色法。结果对照组人群中精子DNA碎片指数和Hcy水平的中位数分别为33%[95%CI(29.0%~34.4%)]和13.2μmol/L[95%CI(12.4μmol/L~14.2μmol/L)],而在严重生精障碍组中这两个指标分别为21%[95%CI(19.0%~24.0%)]和8.9μmol/L[95%CI(8.4μmol/L~9.4μmol/L)],这两个项目的检测结果对照组均高于严重生精障碍组,差异有统计学意义(t=6.793~7.543,P=0.000)。精子存活率正常对照组和严重生精障碍组分别为71%[95%CI(67.8%~75.1%)]和57%[95%CI(52.3%~58.0%)],差异有统计学意义(t=-8.475,P=0.000)。精子DNA碎片指数与血清Hcy水平、精子浓度呈正相关,Passing-Bablok回归方程分别为:Y=10.705+0.053X,Y=21.071+0.286X,而Hcy水平和精子浓度呈负相关趋势。结论 Hcy水平和精子DNA碎片指数的升高,可能是严重生精障碍男性的重要病因,但其具体机制有待进一步研究。
Objective To investigate the relationship between the homocysteine, sperm DNA fragmentation index and sperm counts of male with severe impaired spermatoqenesis. Methods From December 2015 to February 2017,56 male patients with severe impaired spermatoqenesis were enrolled in the study. The patients were divided into two groups according to the WHO criteria:severe oligozoospermia and azoospermia group(n=25) and oligoasthenoteratozoospermia group(n=31),and the control group was a male with no reproductive impairment(n = 27). The sperm parameters were analyzed by using the computer automatic semen analyzer, sperm DNA fragmentation index and serum Hcy level were detected by sperm chromatin diffusion method and enzyme colorimetric method. Results The median of Sperm DNA fragmentation index and homocysteine level in control groups were 33% [95%CI(29. 0% ~34. 4%)] and 13. 2 μmol/L [95%CI(12. 4 μmol/L~14. 2μmol/L)],and in severe spermatogenesis groups in these two indicators were 21% [95%CI(19. 0% ~24. 0%)] and 8. 9 mol/L [95%CI(8. 4 μmol/L~9. 4 μmol/L)], respectively. The results of these two items were higher than the control group,the difference was statistically significant(t=6. 793~7. 543,P = 0. 000). Sperm survival rate in normal control group and severe spermatogenesis group was 71% [95%CI(67. 8%~75.1%)] and 57% [95%CI(52. 3% ~58. 0%)],respectively,and the difference was statistically significant(t=-8. 475,P=0. 000). Sperm DNA fragmentation index was positively correlated with serum Hcy level and sperm concentration,Passing-Bablok regression analysis was:Y=10. 705+0. 053 X,Y=21. 071 + 0. 286 X,and Hcy level was negatively correlated with sperm concentration. Conclusion The increase of Hcy level and sperm DNA fragmentation index may be an important cause of male with severe impaired spermatoqenesis,but the specific mechanism remains to be further studied.
Objective To investigate the relationship between the homocysteine, sperm DNA fragmentation index and sperm counts of male with severe impaired spermatoqenesis. Methods From December 2015 to February 2017,56 male patients with severe impaired spermatoqenesis were enrolled in the study. The patients were divided into two groups according to the WHO criteria:severe oligozoospermia and azoospermia group(n=25) and oligoasthenoteratozoospermia group(n=31),and the control group was a male with no reproductive impairment(n = 27). The sperm parameters were analyzed by using the computer automatic semen analyzer, sperm DNA fragmentation index and serum Hcy level were detected by sperm chromatin diffusion method and enzyme colorimetric method. Results The median of Sperm DNA fragmentation index and homocysteine level in control groups were 33% [95%CI(29. 0% ~34. 4%)] and 13. 2 μmol/L [95%CI(12. 4 μmol/L~14. 2μmol/L)],and in severe spermatogenesis groups in these two indicators were 21% [95%CI(19. 0% ~24. 0%)] and 8. 9 mol/L [95%CI(8. 4 μmol/L~9. 4 μmol/L)], respectively. The results of these two items were higher than the control group,the difference was statistically significant(t=6. 793~7. 543,P = 0. 000). Sperm survival rate in normal control group and severe spermatogenesis group was 71% [95%CI(67. 8%~75.1%)] and 57% [95%CI(52. 3% ~58. 0%)],respectively,and the difference was statistically significant(t=-8. 475,P=0. 000). Sperm DNA fragmentation index was positively correlated with serum Hcy level and sperm concentration,Passing-Bablok regression analysis was:Y=10. 705+0. 053 X,Y=21. 071 + 0. 286 X,and Hcy level was negatively correlated with sperm concentration. Conclusion The increase of Hcy level and sperm DNA fragmentation index may be an important cause of male with severe impaired spermatoqenesis,but the specific mechanism remains to be further studied.
引文
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[9]赵铭佳,周善杰,袁冬,等.正常成年男性精浆同型半胱氨酸浓度及其与精液参数关联性研究[J].生殖医学杂志,2014,23(2):116-120.Zhao MJ,Zhou SJ,Yuan D,et al.Seminal plasma homocysteine levels and the correlation with semen paramerers in normal young men[J].Journal of Reproductive Medicine,2014,23(2):116-120.
[10]Wong WY,Merkus HM,Thomas CM,et al.Effects of folic acid and zinc sulfate on male factor subfertility:a double-blind,randomized,placebo-controlledtrial[J].Fertility Sterility,2002,77(3):491-498.
[11]邱毅,张丽红,王磊光,等.精子染色质扩散实验检测男性不育患者精子DNA碎片[J].国际生殖健康/计划生育杂志,2008,27(6):387-389,后插1.Qiu Y,Zhang LH,Wang LG,et al.Determination of sperm DNA fragmentation in infertile males by sperm chromatin dispersion test[J].Journal of International Reproductive Health/Family Planning,2008,27(6):387-389,后插1.
[12]Lin MH,Kuo-Kuang LR,Li SeeH,et al.Sperm chromatin structure assay parameters are not related to fertilization rates,embryo quality,and pregnancy rates in in vitro fertilization and intracytoplasmic sperm injection,but might be related to spontaneous abortion rates[J].Fertility&Sterility,2008,90(2):352-359.
[13]戈一峰,汪春晖,欧阳罗璇,等.少和/或弱精子症患者血浆同型半胱氨酸的测定及意义[J].中华男科学杂志,2008,14(12):1112-1114.Ge YF,Wang CH,Ouyang LX,et al.Determination of plasma homocysteine in oligospermia and/or asthenospermia patients[J].National Journal of Andrology,2008,14(12):1112-1114.
[14]张德庆,张萌,李忠培,等.解脲支原体感染对男性不育者精浆活性氧与细胞因子的影响[J].现代检验医学杂志,2016,31(1):44-46.Zhang DQ,Zhang M,Li ZP,et al.Influence of seminal plasma reactive oxygen species and cell factors in infertile men with ureaplasma urealyticum infection[J].J Mod Lab Med,2016,31(1):44-46.
[15]Amiri I,Rabiee S,Goodarzi MT,et al.Assessment of correlation between homocysteine concen-tration in follicular fluid and oocyte and embryo quality in polycystic ovary syndrome patients under-going assisted reproductive technology[J].Scientific Journal of Hamadan University of Medical Sciences,2013,19(4):11-19.
[16]杨译,姜辉.精子DNA损伤与男性不育的关系[J].中国男科学杂志,2011,25(12):67-69.Yang Y,Jiang H.The relationship between sperm DNA damage and male infertility[J].Chinese Journal of Andrology,2011,25(12):67-69.
[2]Wu H,Sun L,Wen Y,et al.Major spliceosome defects cause male infertility and are associated with nonobstructive azoospermia in humans[J].Proc Natl Acad Sci USA,2016,113(15):4134-4139.
[3]Diao R,Fok KL,Chen H,et al.Deficient human betadefensin 1 underlies male infertility associated with poor sperm motility and genital tract infection[J].Sci Transl Med,2014,6(249):249.
[4]Ebisch IM,Peters WH,Thomas CM,et al.Homocysteine,glutathione and related thiols affect fertility parameters in the(sub)fertile couple[J].Human Reproduction,2006,21(7):1725-1733.
[5]Molloy AM,Brody LC,Mills JL,et al.The search for genetic polymorphisms in the homocysteine/folate pathway that contribute to the etiology of human neural tube defects[J].Birth Defects Research Part A Clinical Molecular Teratology,2009,85(4):285-294.
[6]邱毅,王苏梅,张丽红,等.精子染色质扩散实验检测精索静脉曲张及不明原因不育患者精子DNA碎片[J].生殖医学杂志,2008,17(6):465-468.Qiu Y,Wang SM,Zhang LH,et al.Determination of sperm DNA fragmentation in unexplained infertile males and in infertile males with varicocele by sperm chromatin dispersion test[J].Journal of Reproductive Medicine,2008,17(6):465-468.
[7]杨译,姜辉,张海娇,等.男性不育患者年龄与精子DNA碎片和精液常规参数的相关性分析[J].中国性科学,2012,21(2):17-19.Yang Y,Jiang H,Zhang HQ,et al.Correlation of age,sperm DNA fragmentation with semen parameters in infertile males[J].Chinese Journal of Human Sexuality,2012,21(2):17-19.
[8]孙超,徐志鹏,石亮,等.不育症患者精子DNA碎片化指数与精子常规参数关系的研究[J].南京医科大学学报(自然科学版),2011,31(4):565-567,570.Sun C,Xu ZP,Shi L,et al.Research on the relationship between sperm DNA fragmentation and semen parameters of infertile men[J].Acta University Medicinalis Nanjing(Natural Sciences),2011,31(4):565-567,570.
[9]赵铭佳,周善杰,袁冬,等.正常成年男性精浆同型半胱氨酸浓度及其与精液参数关联性研究[J].生殖医学杂志,2014,23(2):116-120.Zhao MJ,Zhou SJ,Yuan D,et al.Seminal plasma homocysteine levels and the correlation with semen paramerers in normal young men[J].Journal of Reproductive Medicine,2014,23(2):116-120.
[10]Wong WY,Merkus HM,Thomas CM,et al.Effects of folic acid and zinc sulfate on male factor subfertility:a double-blind,randomized,placebo-controlledtrial[J].Fertility Sterility,2002,77(3):491-498.
[11]邱毅,张丽红,王磊光,等.精子染色质扩散实验检测男性不育患者精子DNA碎片[J].国际生殖健康/计划生育杂志,2008,27(6):387-389,后插1.Qiu Y,Zhang LH,Wang LG,et al.Determination of sperm DNA fragmentation in infertile males by sperm chromatin dispersion test[J].Journal of International Reproductive Health/Family Planning,2008,27(6):387-389,后插1.
[12]Lin MH,Kuo-Kuang LR,Li SeeH,et al.Sperm chromatin structure assay parameters are not related to fertilization rates,embryo quality,and pregnancy rates in in vitro fertilization and intracytoplasmic sperm injection,but might be related to spontaneous abortion rates[J].Fertility&Sterility,2008,90(2):352-359.
[13]戈一峰,汪春晖,欧阳罗璇,等.少和/或弱精子症患者血浆同型半胱氨酸的测定及意义[J].中华男科学杂志,2008,14(12):1112-1114.Ge YF,Wang CH,Ouyang LX,et al.Determination of plasma homocysteine in oligospermia and/or asthenospermia patients[J].National Journal of Andrology,2008,14(12):1112-1114.
[14]张德庆,张萌,李忠培,等.解脲支原体感染对男性不育者精浆活性氧与细胞因子的影响[J].现代检验医学杂志,2016,31(1):44-46.Zhang DQ,Zhang M,Li ZP,et al.Influence of seminal plasma reactive oxygen species and cell factors in infertile men with ureaplasma urealyticum infection[J].J Mod Lab Med,2016,31(1):44-46.
[15]Amiri I,Rabiee S,Goodarzi MT,et al.Assessment of correlation between homocysteine concen-tration in follicular fluid and oocyte and embryo quality in polycystic ovary syndrome patients under-going assisted reproductive technology[J].Scientific Journal of Hamadan University of Medical Sciences,2013,19(4):11-19.
[16]杨译,姜辉.精子DNA损伤与男性不育的关系[J].中国男科学杂志,2011,25(12):67-69.Yang Y,Jiang H.The relationship between sperm DNA damage and male infertility[J].Chinese Journal of Andrology,2011,25(12):67-69.