锌、铜和钴水平升高与子宫内膜异位症风险增加有关:一项病例对照研究的结果

Elevated levels of Zn, Cu and Co are associated with an increased risk of endometriosis: Results from a casecontrol study

锌、铜和钴水平升高与子宫内膜异位症风险增加有关:一项病例对照研究的结果

Authors：Su X, Yue X, Zhang Y, Shen L, Zhang H, Wang X, Yin T, Zhang H, Peng J, Wang X, Zou W, Liang D, Du Y, Liu Y, Cao Y, Ji D, Liang C.

Source：Ecotoxicol Environ Saf.

DOI：10.1016/j.ecoenv.2024.115932

Abstract

BACKGROUND: Endometriosis is a common gynecological disease that affects approximately 5 % of reproductive-aged women. Zinc (Zn), selenium (Se), copper (Cu), cobalt (Co) and molybdenum (Mo) are essential trace elements and are very important for human health. However, studies on the relationship between mixtures of essential trace elements and the risk of endometriosis are limited and inconsistent. In particular, studies confirming the association via different sample types are limited.

OBJECTIVE: This study aimed to investigate the associations between Zn, Se, Cu, Co and Mo concentrations in blood and follicular fluid (FF) and endometriosis risk in a Chinese population.

METHODS: A total of 609 subjects undergoing in vitro fertilization (IVF) were recruited; 836 samples were analyzed, including 451 blood samples (234 controls and 217 cases) and 385 FF samples (203 controls and 182 cases). In addition, 227 subjects provided both blood and FF samples. Zn, Se, Cu, Co and Mo concentrations in blood and FF were quantified via inductively coupled plasma-mass spectrometry (ICP-MS). The associations between the levels of Zn, Se, Cu, Co and Mo and the risk of endometriosis were assessed using single-element models (logistic regression models), and the combined effect of the trace elements on endometriosis risk was assessed using multielement models (Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression).

RESULTS: Based on the single-element models, significant associations of Zn concentrations in blood (high-level vs. low-level group: aOR = 14.17, 95 % CI: 7.31, 27.50) and FF (first tertile vs. second tertile group: aOR = 0.34, 95 % CI: 0.16, 0.71; third tertile vs. second tertile group: aOR = 2.32, 95 % CI: 1.38, 3.91, respectively) and Co concentrations in blood (first tertile vs. second tertile group, aOR = 0.24, 95 % CI: 0.12, 0.48) and FF (third tertile vs. second tertile group: aOR = 3.87, 95 % CI: 2.19, 6.84) with endometriosis risk were found after adjustment for all confounders. In FF, Cu and Mo levels were significantly greater among the cases than among the controls, with a positive association with endometriosis risk (Cu (first tertile vs. second tertile group: aOR = 0.39, 95 % CI: 0.19, 0.81; third tertile vs. second tertile group: aOR = 2.73, 95 % CI: 1.61, 4.66, respectively) and Mo (high-level vs. low-level group: aOR = 14.93, 95 % CI: 7.16, 31.12)). However, similar associations between blood Cu and Mo levels and endometriosis risk were not found. In addition, the levels of these five essential trace element mixtures in blood and in FF were significantly and positively associated with endometriosis risk according to the BKMR analyses; the levels of Zn and Cu in blood and the levels of Mo in FF were significantly related to the risk of endometriosis, and the posterior inclusion probabilities (PIPs) were 1.00, 0.99 and 1.00 for Zn and Cu levels in blood and Mo levels in FF, respectively. Furthermore, Zn and Mo were the highest weighted elements in blood and FF, respectively, according to WQS analyses.

CONCLUSION: The risk of endometriosis was associated with elevated levels of several essential trace elements (Zn, Cu and Co). Elevated levels of these elements may be involved in the pathomechanism of endometriosis. However, further studies with larger sample sizes will be necessary to confirm these associations.

摘要

背景：子宫内膜异位症是一种常见的妇科疾病，影响大约 5% 的育龄妇女。锌（Zn）、硒（Se）、铜（Cu）、钴（Co）和钼（Mo）是人体必需的微量元素，对人体健康非常重要。然而，关于必需微量元素混合物与子宫内膜异位症风险之间关系的研究是有限且不一致的。特别是，通过不同样本类型证实这种关联的研究是有限的。

目的：探讨中国人群血液和滤泡液（FF）中Zn、Se、Cu、Co和Mo浓度与子宫内膜异位症风险的关系。

方法：共招募609名接受体外受精（IVF）的受试者;共分析836份样本，其中血样451份（对照234例，217例）和FF样本385份（对照203例，182例）。此外，227名受试者提供了血液和FF样本。通过电感耦合等离子体质谱（ICP-MS）对血液和FF中的Zn、Se、Cu、Co和Mo浓度进行定量分析。采用单元素模型（logistic回归模型）评估Zn、Se、Cu、Co、Mo水平与子宫内膜异位症风险的相关性，并使用多元素模型（贝叶斯核机回归（BKMR）和加权分位数和（WQS）回归）评估微量元素对子宫内膜异位症风险的综合影响。

结果：基于单元素模型，血液中的锌浓度（高水平与低水平组：aOR = 14.17,95% CI：7.31,27.50）和 FF（第一三分位数与第二三分位数组：aOR = 0.34,95% CI：0.16,0.71;第三三分位数与第二三分位数组：aOR = 2.32,95% CI：分别为 1.38,3.91）和 Co在调整所有混杂因素后，发现血液中具有子宫内膜异位症风险的浓度（第一三分位数与第二三分位数组，aOR = 0.24,95% CI：0.12,0.48）和 FF（第三三分位数与第二三分位数组：aOR = 3.87,95% CI：2.19,6.84）中具有子宫内膜异位症风险。在FF中，病例中的Cu和Mo水平显著高于对照组，与子宫内膜异位症风险呈正相关（Cu（第一三分位数组与第二三分位数组：aOR=0.39,95%CI：0.19,0.81;第三三分位数与第二三分位数组：aOR=2.73,95%CI：分别为1.61,4.66）和Mo（高水平组与低水平组：aOR=14.93， 95% CI：7.16,31.12））。然而，没有发现血液中Cu和Mo水平与子宫内膜异位症风险之间的类似关联。此外，根据 BKMR 分析，血液和 FF 中这五种必需微量元素混合物的水平与子宫内膜异位症风险显着呈正相关;血液中Zn和Cu水平以及FF中Mo水平与子宫内膜异位症风险显著相关，血液中Zn和Cu水平以及FF中Mo 水平的后验包涵体概率（PIPs）分别为1.00、0.99和1.00。此外，根据WQS分析，Zn和Mo分别是血液和FF中权重最高的元素。

结论：子宫内膜异位症的风险与几种必需微量元素（Zn、Cu和Co）水平升高有关。这些元素水平升高可能与子宫内膜异位症的病理机制有关。然而，需要对更大的样本量进行进一步的研究来证实这些关联。