重金属混合暴露与育龄男性精浆果糖的关联

Relationship between mixed exposure to heavy metals and seminal fructose in men of childbearing age

[背景]人体通常同时暴露于多种重金属环境之中,不同种类和浓度的重金属元素在人体吸收和代谢过程中可能产生复杂的交互作用。研究表明金属暴露可能导致精液质量损伤,精浆果糖是精子运动的重要能量来源,分析重金属混合暴露与精浆果糖的关联,对探索金属暴露致精液质量损伤的机制具有一定的意义。[目的]了解河南省濮阳市育龄男性常见重金属暴露现状,探索分析重金属混合暴露及其交互作用与育龄男性精浆果糖水平的相关性。从濮阳市妇幼保健院生殖中心招募志愿者进行横断面研究,利用问卷调查研究对象的一般人口学特征、吸烟、饮酒等资料。采集精液样本,检测精浆中钒(V)、锰(Mn)、钴(Co)、镍(Ni)、锌(Zn)、硒(Se)、银(Ag)、镉(Cd)、钡(Ba)、铊(Tl)、铁(Fe)、铅(Pb)12种金属浓度与精浆果糖水平。在校正混杂因素后使用贝叶斯核机器回归(BKMR)模型评估精浆重金属混合暴露及其交互作用对精浆果糖的影响。共825名成年男性纳入本次研究,V、Mn、Co、Ni、Zn、Se、Ag、Cd、Ba、Tl、Fe、Pb共12种金属精浆暴露浓度M(P_(25),P_(75))分别为0.39(0.28,0.54)、12.31(8.92,17.52)、0.26(0.18,0.38)、5.15(3.32,8.64)、182159.80(121847.80,199144.50)、13.61(10.55,17.68)、0.03(0.02,0.04)、0.34(0.27,0.46)、8.64(5.94,13.43)、0.06(0.05,0.08)、168.74(114.17,259.45)、1.69(1.15,2.36)μg·L^(-1)。Spearman相关分析结果提示,精浆V、Mn、Co、Zn、Se、Ba、Tl、Fe与精浆果糖之间呈现负相关关系(P<0.05),r(95%CI)分别为-0.044(-0.087~-0.001)、-0.129(-0.171~-0.087)、-0.055(-0.099~-0.012)、-0.099(-0.143~-0.056)、-0.053(-0.097~-0.010)、-0.068(-0.111~-0.025)、-0.095(-0.138~-0.052)、-0.082(-0.125~-0.039)。多重线性回归结果提示,精浆Cd、Mn、Zn、Ag、Ba、Tl、Fe暴露与精浆果糖之间呈现负相关关系(P<0.05),β(95%CI)分别为-0.551(-0.956~-0.147)、-0.315(-0.419~-0.212)、-0.187(-0.272~-0.103)、-0.161(-0.301~-0.021)、-0.188(-0.314~-0.062)、-1.159(-2.170~-0.147)、-0.153(-0.230~-0.076)。通过BKMR模型分析发现精浆果糖水平随着精浆金属混合暴露浓度的上升而呈下降趋势。与所有金属暴露量均固定于P50相比,所有金属暴露量均固定于P_(75)时精浆果糖水平下降了0.2374个单位。其中精浆Zn[后验包含概率(PIPs)=1.0000]对精浆果糖的效应最强,其次是Mn(PIPs=0.5872)、Se(PIPs=0.5656)、Ba(PIPs=0.5398)。单变量暴露-反应曲线显示精浆中Ba、Mn与精浆果糖存在负向的近似线性相关关系,金属Se与精浆果糖存在正向线性相关关系,金属Zn与精浆果糖呈近似倒U型相关。尚未发现金属之间的效应存在明显的交互作用。[结论]金属混合暴露可能导致精浆果糖水平的下降,其中Zn、Mn、Se、Ba起重要作用。Mn与Zn暴露均可能降低精浆果糖水平,而Se可能提高精浆果糖水平,不过Zn暴露与精浆果糖水平之间可能存在阈值效应,尚未发现不同金属作用于精浆果糖时存在交互作用。

[Background]The human body is usually exposed to a variety of heavy metals at the same time,and different types and concentrations of heavy metals may have complex interactions during their absorption and metabolism in the human body.Seminal fructose is an important energy source for sperm movement.A large number of studies have shown that metal exposure may impair semen quality,and seminal fructose is an important factor affecting male reproduction,so it is necessary to investigate the relationship between mixed heavy metal exposure and seminal fructose to explore the mechanism of semen quality damage caused by metal exposure.[Objective]To understand the status of common heavy metal exposure in men of childbearing age in Puyang City,Henan Province,and to study the relationship between mixed exposure to heavy metals and seminal fructose,as well as potential interactions among heavy metals.[Methods]Volunteers were recruited from the Puyang Maternal and Child Health Hospital Reproductive Center for a cross-sectional survey on general demographic characteristics,smoking,alcohol consumption,and other information.Semen samples were collected to detect 12 metals such as vanadium(V),manganese(Mn),cobalt(Co),nickel(Ni),zinc(Zn),selenium(Se),silver(Ag),cadmium(Cd),barium(Ba),thallium(Tl),iron(Fe),and lead(Pb)in seminal plasma and seminal fructose.After correcting for selected confounding factors,a Bayesian kernel machine regression(BKMR)model was used to evaluate the impact of seminal plasma heavy metal mixed exposure and its interactions on seminal fructose.[Results]A total of 825 adult males were enrolled.The concentrations in M(P_(25),P_(75))of V,Mn,Co,Ni,Zn,Se,Ag,Cd,Ba,Tl,Fe,and Pb in seminal plasma were 0.39(0.28,0.54),12.31(8.92,17.52),0.26(0.18,0.38),5.15(3.32,8.64),182159.80(121847.80,199144.50),13.61(10.55,17.68),0.03(0.02,0.04),0.34(0.27,0.46),8.64(5.94,13.43),0.06(0.05,0.08),168.74(114.17,259.45),and 1.69(1.15,2.36)μg·L^(-1) respectively.The Spearman correlation results indicated that there was a negative correlation between V,Mn,Co,Zn,Se,Ba,Tl,or Fe in seminal plasma and seminal fructose(P<0.05),and the values of r(95%CI)were-0.044(-0.087,-0.001),-0.129(-0.171,-0.087),-0.055(-0.099,-0.012),-0.099(-0.143,-0.056),-0.053(-0.097,-0.010),-0.068(-0.111,-0.025),-0.095(-0.138,-0.052),and-0.082(-0.125,-0.039),respectively.The results of multiple linear regression indicated that there was a negative correlation between the exposure level of Cd,Mn,Zn,Ag,Ba,Tl,or Fe in seminal plasma and seminal fructose(P<0.05),the values of associatedβ(95%CI)were-0.551(-0.956,-0.147),-0.315(-0.419,-0.212),-0.187(-0.272,-0.103),-0.161(-0.301,-0.021),-0.188(-0.314,-0.062),-1.159(-2.170,-0.147),and-0.153(-0.230,-0.076),respectively.The BKMR model analysis showed that seminal fructose level decreased with the increase of plasma metal mixed exposure concentration.Compared with all metal exposure at P50,the seminal fructose level decreased by 0.2374 units when all metal exposure was at P_(75).Seminal plasma Zn[posterior inclusion probabilities(PIPs)=1.0000]had the strongest effect on seminal fructose,followed by Mn(PIPs=0.5872),Se(PIPs=0.5656),and Ba(PIPs=0.5398).The univariate exposure-response curve showed a negative approximate linear correlations between Ba or Mn and seminal fructose,a positive linear correlation between Se and seminal fructose,and an approximate inverted U-shaped association between Zn and seminal fructose.No significant interaction between studied metals was found.[Conclusion]Mixed metal exposure may lead to decrease of seminal fructose,in which Zn,Mn,Se,and Ba may play an important role.Mn and Zn exposure may reduce the level of seminal fructose,Se may increase the level of seminal fructose,and there may be a threshold effect between Zn exposure and seminal fructose level.No interaction between different metals on seminal fructose is found.