Sperm mitochondrial DNA biomarkers and couple fecundity.
Sperm mitochondrial DNA biomarkers and couple fecundity.
复制标题
精子线粒体 DNA 生物标志物和夫妻生育力。
DOI：
10.1093/humrep/deaa191
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Pilsner,JRichard
中科院分区：
文献类型：
--
作者：
Rosati,AllysonJ;Whitcomb,BrianW;Brandon,Nicole;BuckLouis,GermaineM;Mumford,SunniL;Schisterman,EnriqueF;Pilsner,JRichard
研究问题：精子线粒体DNA测量能预测一般人群中夫妇的怀孕概率吗？摘要回答：精子线粒体DNA拷贝数（mtDNAn）高的人周期特异性妊娠的几率降低50%，12个月内妊娠的几率降低18%。已知内容精液参数被发现不能很好地预测生殖成功，但它是男性不育最普遍的诊断工具。精子mtDNA Acn和线粒体DNA缺失增加研究设计、规模、持续时间：2005年至2009年，对美国16个县的夫妇停止避孕怀孕进行为期16个月的前瞻性队列研究。方法采用三重探针定量PCR技术检测384份精液标本中精子mtDNA Acn和mtDNA del的含量。1年内怀孕的概率进行了比较，线粒体DNA，离散时间比例风险模型被用来评估与怀孕时间（TTP）的关系与调整的协变量。主要结果和角色的机会较高的精子mtDNA与较低的怀孕概率在12个月内，更长的TTP。在按四分位数（Q）进行的未校正比较中，Q4的妊娠概率为63.5%（95% CI：53.1%至73.1%），而Q1的妊娠概率为82.3%（95% CI：73.2%至89.9%）（P= 0.002）。在生存分析中观察到类似的结果，调整协变量，以估计生殖力比值比（FO）比较四分位数的mtDNA。相对于mtDNA的Q1，Q2的FORs（95%CI）为0.78（0.52至1.16），Q3为0.65（0.44 ~ 0.96）和Q4为0.55（0.37 ~ 0.81），且随着mtDNAn四分位数的增加，受精力下降的趋势具有统计学意义（FOR/logmtDNAn = 0.37;P< 0.001）。精子mtDNAdel与TTP无关。排除的原因这项前瞻性队列研究主要由白人男性和女性组成，因此需要大量不同的队列来证实精子mtDNA与其他种族夫妇怀孕成功之间的关系。我们的研究结果表明，精子mtDNA Acn可作为男性生殖健康和妊娠成功概率的生物标志物，研究资金/竞争利益（S）这项工作的一部分由美国国立卫生研究院国家环境健康科学研究所（R 01-ES 028298; PI：J. R. P.）和Eunice Kennedy Shriver National Institute of Child Health and Human Development，National Institutes of Health，Bethesda，马里兰州的校内研究计划（合同号N 01-HD-3-3355、N 01-HD-3-3356和N 01-HD-3-3358）。提交人声明没有利益冲突。
STUDY QUESTIONDo sperm mitochondrial DNA measures predict probability of pregnancy among couples in the general population?SUMMARY ANSWERThose with high sperm mitochondrial DNA copy number (mtDNAcn) had as much as 50% lower odds of cycle-specific pregnancy, and 18% lower probability of pregnancy within 12 months.WHAT IS KNOWN ALREADYSemen parameters have been found to poorly predict reproductive success yet are the most prevalent diagnostic tool for male infertility. Increased sperm mtDNAcn and mitochondrial DNA deletions (mtDNAdel) have been associated with decreased semen quality and lower odds of fertilization in men seeking fertility treatment.STUDY DESIGN, SIZE, DURATIONA population-based prospective cohort study of couples discontinuing contraception to become pregnant recruited from 16 US counties from 2005 to 2009 followed for up to 16 months.PARTICIPANTS/MATERIALS, SETTING, METHODSSperm mtDNAcn and mtDNAdel from 384 semen samples were assessed via triplex probe-based quantitative PCR. Probability of pregnancy within 1 year was compared by mitochondrial DNA, and discrete-time proportional hazards models were used to evaluate the relations with time-to-pregnancy (TTP) with adjustment for covariates.MAIN RESULTS AND THE ROLE OF CHANCEHigher sperm mtDNAcn was associated with lower pregnancy probability within 12 months and longer TTP. In unadjusted comparisons by quartile (Q), those in Q4 had a pregnancy probability of 63.5% (95% CI: 53.1% to 73.1%) compared to 82.3% (95% CI: 73.2% to 89.9%) for Q1 (P= 0.002). Similar results were observed in survival analyses adjusting for covariates to estimate fecundability odds ratios (FORs) comparing mtDNAcn in quartiles. Relative to those in Q1 of mtDNAcn, FORs (95% CI) were for Q2 of 0.78 (0.52 to 1.16), Q3 of 0.65 (0.44 to 0.96) and Q4 of 0.55 (0.37 to 0.81), and this trend of decreasing fecundability with increasing mtDNAcn quartile was statistically significant (FOR per log mtDNAcn = 0.37;P< 0.001). Sperm mtDNAdel was not associated with TTP.LIMITATIONS, REASONS FOR CAUTIONThis prospective cohort study consisted primarily of Caucasian men and women and thus large diverse cohorts are necessary to confirm the associations between sperm mtDNAcn and couple pregnancy success in other races/ethnicities.WIDER IMPLICATIONS OF THE FINDINGSOur results demonstrate that sperm mtDNAcn has utility as a biomarker of male reproductive health and probability of pregnancy success in the general population.STUDY FUNDING/COMPETING INTEREST(S)This work was funded in part by the National Institute of Environmental Health Sciences, National Institutes of Health (R01-ES028298; PI: J.R.P.) and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contracts N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). The authors declare no competing interests.TRIAL REGISTRATION NUMBERN/A