精液金属浓度、ESR1基因与精液质量关系

Association of semen metal concentration and estrogen receptor alpha gene with semen quality in human

目的了解男性精液金属浓度、雌激素受体α基因(ESR1)与精液质量之间的关系,为进一步研究金属影响精液质量的可能作用机制提供流行病学基础。方法采用以医院为基础成组病例对照研究方法,选择2016年9月—2017年11月在广东省深圳市某三甲医院生殖医学中心进行精液检查的91例精液质量异常和91名精液质量正常的男性人群进行问卷调查及11种金属浓度和ESR1基因mRNA表达水平检测。结果病例组男性人群精液金属铬(Cr)、锰(Mn)、铜(Cu)和铊(Tl)中位数浓度分别为2.12、9.61、107.00和0.23μg/L,均高于对照组男性人群的1.64、8.18、91.40和0.19μg/L,差异均有统计学意义(均P<0.01);病例组和对照组男性人群ESR1基因mRNA相对表达水平分别为(–0.66±4.85)和(0.63±3.96),差异有统计学意义(t=-1.974,P<0.05)。在控制年龄、体质指数(BMI)和禁欲时间后,多因素非条件logistic回归分析结果显示,精液金属Cr、Mn和Cu最高四分位数浓度组发生精液质量异常的风险分别为最低四分位数浓度组的3.16倍(OR=3.16,95%CI=1.32~7.58)、3.58倍(OR=3.58,95%CI=1.45~8.83)和3.17倍(OR=3.17,95%CI=1.32~7.64),Tl第三四分位数浓度组和最高四分位数浓度组发生精液质量异常的风险分别为最低四分位数浓度组的2.77倍(OR=2.77,95%CI=1.15~6.70)和3.96倍(OR=3.96,95%CI=1.55~10.08);ESR1基因mRNA低表达组发生精液质量异常的风险为高表达组的1.89倍(OR=1.89,95%CI=1.04~3.46)。在控制年龄、BMI和禁欲时间后,多元线性回归分析结果显示,与最低四分位数浓度组相比,金属Tl最高四分位数浓度组与ESR1基因mRNA表达水平呈负相关(b=-2.49,95%CI=-4.44~–0.54)。中介效应分析结果显示,ESR1基因在Tl与精液质量的关系中起部分中介效应,该效应占总效应的18.6%。结论精液金属Cr、Mn、Cu和Tl暴露及ESR1基因mRNA低表达是精液质量的危险因素,精液金属Tl对精液质量的影响部分由ESR1基因介导。

Objective To investigate the association of semen metal concentration and estrogen receptor alpha gene(ESR1)with semen quality in human and to provide epidemiological evidences for researches on mechanism of metal's effect on semen quality.Methods A hospital-based case-control study was conducted among 91 cases and 91 controls with abnormal and normal semen quality recruited from the attendees having semen examination in a reproductive medicine center of a tertiary grade A hospital in Shenzhen city from September 2016 to November 2017.A questionnaire interview and laboratory detection on concentrations of 11 metals and ESR1 expression in semen were carried out in the participants.Results Compared to the controls,the cases had significantly higher median seminal concentration(μg/L)of chromium(Cr:2.12 vs.1.64),manganese(Mn:9.61 vs.8.18),copper(Cu:107.00 vs.91.40),and thallium(Tl:0.23 vs.0.19)(all P<0.01).The relative mRNA expression level of ESR1 gene in the semen of the cases(–0.66±4.85)and the controls(0.63±3.96)was significantly different(t=-1.974,P<0.05).The results of unconditional multivariate logistic regression demonstrated that after adjusting for age,body mass index(BMI)and abstinence time,in contrast to those with the lowest quartile concentrations,the participants with the highest quartile concentration of Cr,Mn and Cu were at increased risk of abnormal semen quality,with the odds ratio(OR)(95%confidence interval[95%CI])of 3.16(1.32-7.58),3.58(1.45-8.83)and 3.17(1.32-7.64),respectively;the participants with the third and the highest quartile concentration of Tl were also at increased risk of abnormal semen quality,with the OR(95%CI)of 2.77(1.15-6.70)and 3.96(1.55-10.08)compared to the participants with the lowest quartile concentration.The participants with a low ESR1 gene expression in semen had an increased risk of abnormal semen quality(OR=1.89,95%CI:1.04-3.46)in comparison with those with a high ESR1 gene expression.The results of multivariate linear regression analysis revealed that in comparison to the lowest quartile concentration,the highest quartile seminal concentration of Tl was reversely correlated with ESR1 gene expression(b=-2.49,95%CI:-4.44-–0.54)after adjusting for age,BMI and abstinence time.Mediation analysis indicated that ESR1 gene expression contributed to a significant proportion of the correlation between Tl and semen quality,accounting for 18.6%of the total effect.Conclusion High metal concentration of Cr,Mn,Cu,and Tl and low expression of ESR1 gene in semen are risk factors for abnormal semen quality.The adverse effect of Tl on semen quality is partially mediated by ESR1 gene expression.