Abstract：
Metal pollution can cause a decline in female fertility, however, previous studies have focused more on the effect of a single metal on fertility. In this study, we evaluated the effect of metal mixtures on female fertility based on nested case-control samples. The plasma levels of 22 metal elements from 180 women were determined by an inductively coupled plasma mass spectrometer (ICP-MS). Minimum absolute contraction and selection operator (LASSO) penalty regression selected metals with the greatest influence on clinical outcome. Logistic regression was used to analyze the correlation between single metals and fertility while a Bayesian kernel function regression (BKMR) model was used to analyze the effect of mixed metals. Eight metals (Calcium (Ca), Chromium (Cr), Cobalt (Co), Copper (Cu), Zinc (Zn), Rubidium (Rb), Strontium (Sr) and Zirconium (Zr)) were selected by LASSO regression for subsequent analysis. After adjusting for covariates, the logistic model showed that Cu (Odds Ratio(OR):0.33, 95% CI: 0.13 - 0.84) and Co (OR:0.38, 95% CI: 0.15 -0.94) caused a significant reduction in fertility, and identified the protective effect of Zn (OR: 2.96, 95% CI:1.21 -7.50) on fertility. Trend tests showed that increased Cr, Cu, and Rb levels were associated with reduced fertility. The BKMR model showed that Cr, Co, Cu, and Rb had a nonlinear relationship with fertility decline when controlling for the concentrations of other metals and suggested that Cu and Cr might exert an influence on fertility. Analysis showed a negative correlation between Cu, Cr, Co, Rb, and fertility, and a positive correlation between Zn and fertility. Furthermore, we found evidence for the interaction between Cu and Cr. Our findings require further validation and may identify new mechanisms in the future.
摘要：
金属污染会导致女性生育能力下降，然而,以前的研究更多地集中在单一金属对生育能力的影响上。在这项研究中,我们基于嵌套病例对照样本评估了金属混合物对女性生育力的影响.通过电感耦合等离子体质谱仪（ICP-MS）测定了来自180名女性的22种金属元素的血浆水平。最小绝对收缩和选择操作者(LASSO)惩罚回归选择对临床后果影响最年夜的金属。使用Logistic回归分析单金属与生育力之间的相关性，同时使用贝叶斯核函数回归（BKMR）模型分析混合金属的影响。八种金属(钙(Ca)，铬(Cr),钴(Co),铜(Cu),锌(Zn),铷(Rb),通过LASSO回归选择锶（Sr）和锆（Zr）用于后续分析。在调整协变量后，Logistic模型显示，Cu（比值比（OR）：0.33，95％CI：0.13-0.84）和Co（OR：0.38，95％CI：0.15-0.94）导致生育率显着降低，并确定了锌对生育能力的保护作用（OR：2.96，95％CI：1.21-7.50）。趋势测试表明，Cr的增加，Cu,Rb水平与生育率降低有关。BKMR模型表明，Cr，Co,Cu,当控制其他金属的浓度时，Rb与肥力下降呈非线性关系，表明Cu和Cr可能对肥力产生影响。分析表明Cu,Cr,Co,Rb,和生育能力，锌与肥力呈正相关。此外，我们发现了Cu和Cr之间相互作用的证据。我们的发现需要进一步验证，并可能在未来确定新的机制。
