Gómez-Olarte Sergio, Mailänder Verena, Castro-Neves Júlia, Stojanovska Violeta, Schumacher Anne, Meyer Nicole, Zenclussen Ana C
Department of Environmental Immunology, Helmholtz Centre for Environmental Research GmbH-UFZ, Permoserstraße 15, 04318, Leipzig, Germany.
Perinatal Immunology, Saxonian Incubator for Clinical Translation (SIKT), Medical Faculty, Leipzig University, Philipp-Rosenthal-Straße 55, 04103, Leipzig, Germany.
Biol Reprod. 2024 Dec 12;111(6):1170-1187. doi: 10.1093/biolre/ioae142.
Endocrine-disrupting chemicals are natural and synthetic compounds found ubiquitously in the environment that interfere with the hormonal-immune axis, potentially impacting human health and reproduction. Exposure to endocrine-disrupting chemicals has been associated with numerous health risks, such as neurodevelopmental disorders, metabolic syndrome, thyroid dysfunction, infertility, and cancers. Nevertheless, the current approach to establishing causality between these substances and disease outcomes has limitations. Epidemiological and experimental research on endocrine-disrupting chemicals faces challenges in accurately assessing chemical exposure and interpreting non-monotonic dose response curves. In addition, most studies have focused on single chemicals or simple mixtures, overlooking complex real-life exposures and mechanistic insights, in particular regarding endocrine-disrupting chemicals' impact on the immune system. The ENDOMIX project, funded by the EU's Horizon Health Program, addresses these challenges by integrating epidemiological, risk assessment, and immunotoxicology methodologies. This systemic approach comprises the triangulation of human cohort, in vitro, and in vivo data to determine the combined effects of chemical mixtures. The present review presents and discusses current literature regarding human reproduction in the context of immunotolerance and chemical disruption mode of action. It further underscores the ENDOMIX perspective to elucidate the impact of endocrine-disrupting chemicals on immune-reproductive health.
内分泌干扰化学物质是在环境中普遍存在的天然和合成化合物，它们会干扰激素-免疫轴，可能影响人类健康和生殖。接触内分泌干扰化学物质与众多健康风险相关，如神经发育障碍、代谢综合征、甲状腺功能障碍、不孕不育和癌症。然而，目前确定这些物质与疾病结果之间因果关系的方法存在局限性。关于内分泌干扰化学物质的流行病学和实验研究在准确评估化学物质暴露和解释非单调剂量反应曲线方面面临挑战。此外，大多数研究都集中在单一化学物质或简单混合物上，忽视了复杂的现实生活暴露情况和作用机制，特别是关于内分泌干扰化学物质对免疫系统的影响。由欧盟地平线健康计划资助的ENDOMIX项目通过整合流行病学、风险评估和免疫毒理学方法来应对这些挑战。这种系统方法包括对人类队列、体外和体内数据进行三角测量，以确定化学混合物的综合影响。本综述介绍并讨论了当前关于免疫耐受和化学物质干扰作用模式背景下人类生殖的文献。它进一步强调了ENDOMIX项目的观点，以阐明内分泌干扰化学物质对免疫-生殖健康的影响。
