Abstract

Background:

Growing epidemiological evidence suggests that organochlorine chemicals (OCCs), including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may play a role in the pathogenesis of endometriosis.

Objectives:

We aimed to systematically review the experimental evidence (in vivo and in vitro) on the associations between exposure to OCCs and endometriosis-related end points.

Methods:

A systematic review protocol was developed following the National Toxicology Program /Office of Health Assessment and Translation (NTP/OHAT) framework and managed within a web-based interface. In vivo studies designed to evaluate the impact of OCCs on the onset or progression of endometriosis and proliferation of induced endometriotic lesions were eligible. Eligible in vitro studies included single-cell and co-culture models to evaluate the proliferation, migration, and/or invasion of endometrial cells. We applied the search strings to PubMed, Web of Science, and Scopus®. A final search was performed on 24 June 2020. Assessment of risk of bias and the level of evidence and integration of preevaluated epidemiological evidence was conducted using NTP/OHAT framework

Results:

Out of 812 total studies, 39 met the predetermined eligibility criteria (15 in vivo, 23 in vitro, and 1 both). Most studies ($n=27$) tested TCDD and other dioxin-like chemicals. In vivo evidence supported TCDD’s promotion of endometriosis onset and lesion growth. In vitro evidence supported TCDD’s promotion of cell migration and invasion, but there was insufficient evidence for cell proliferation. In vitro evidence further supported the roles of the aryl hydrocarbon receptor and matrix metalloproteinases in mediating steroidogenic disruption and inflammatory responses. Estrogen interactions were found across studies and end points.

Conclusion:

Based on the integration of a high level of animal evidence with a moderate level of epidemiological evidence, we concluded that TCDD was a known hazard for endometriosis in humans and the conclusion is supported by mechanistic in vitro evidence. Nonetheless, there is need for further research to fill in our gaps in understanding of the relationship between OCCs and their mixtures and endometriosis, beyond the prototypical TCDD. https://doi.org/10.1289/EHP8421

中文翻译：

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有机氯化学品暴露与子宫内膜异位症之间的关联：对实验研究和流行病学证据整合的系统评价

摘要

背景：

越来越多的流行病学证据表明，包括 2,3,7,8-四氯二苯并对二恶英 (TCDD) 在内的有机氯化学品 ( OCC ) 可能在子宫内膜异位症的发病机制中发挥作用。

目标：

我们旨在系统地回顾关于暴露于 OCC 与子宫内膜异位症相关终点之间关联的实验证据（体内和体外）。

方法：

根据国家毒理学计划/健康评估和翻译办公室 (NTP/OHAT) 框架制定了系统审查协议，并在基于网络的界面中进行管理。旨在评估 OCC 对子宫内膜异位症的发生或进展以及诱发的子宫内膜异位症病变增殖的影响的体内研究是合格的。符合条件的体外研究包括单细胞和共培养模型，以评估子宫内膜细胞的增殖、迁移和/或侵袭。我们将搜索字符串应用于 PubMed、Web of Science 和 Scopus®。最终检索于 2020 年 6 月 24 日进行。使用 NTP/OHAT 框架评估偏倚风险和证据水平以及整合预先评估的流行病学证据

结果：

在 812 项研究中，39 项符合预定的资格标准（15 项体内研究、23项体外研究和 1 项两​​者兼有）。大多数研究（$n=27$) 测试了 TCDD 和其他类似二恶英的化学物质。体内证据支持 TCDD 促进子宫内膜异位症发作和病变生长。体外证据支持 TCDD 促进细胞迁移和侵袭，但细胞增殖的证据不足。体外证据进一步支持芳烃受体和基质金属蛋白酶在介导类固醇生成破坏和炎症反应中的作用。跨研究和终点发现雌激素相互作用。

结论：

基于高水平的动物证据与中等水平的流行病学证据的整合，我们得出结论，TCDD 是人类子宫内膜异位症的已知危害，并且该结论得到体外机械证据的支持。尽管如此，除了典型的 TCDD 之外，还需要进一步的研究来填补我们对 OCC 及其混合物与子宫内膜异位症之间关系的理解空白。https://doi.org/10.1289/EHP8421