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The concealment and accumulation of environmental hazards, and their interactions with the endogenous immune network, have long been underappreciated. As the central organ for sperm maturation and motility acquisition, the epididymis plays a vital role in male fertility, and the homeostasis of the epididymal immune microenvironment (EIM) is essential. Nevertheless, a systematic synthesis of common environmental hazards and their impact on EIM, which can lead to male infertility, remains lacking. This review comprehensively summarizes the composition, functionality, and key characteristics of the EIM and underscores its critical role in preserving male reproductive health. We further evaluate and delineate the disruption of EIM homeostasis resulting from major categories of environmental exposures\u2014including chemical, physical, biological, and behavioral hazards\u2014and discuss their shared pathophysiological mechanisms. By integrating evidence linking environmental insults, EIM dysregulation, and male infertility, this work aims to identify pivotal molecular mechanisms from an immunological perspective. The findings provide a mechanistic foundation for the development of targeted interventions and preventive strategies against environmental hazard-induced male infertility.<\/jats:p>","DOI":"10.3390\/toxics14020171","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:14:32Z","timestamp":1771236872000},"page":"171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Common Environmental Hazards and Male Infertility: Effects on Epididymal Immune Microenvironment"],"prefix":"10.3390","volume":"14","author":[{"given":"Xin-Run","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei 230032, China"},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, School of Public Health, Wannan Medical College, Wuhu 241000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei 230032, China"},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye-Xin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei 230032, China"},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Fang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei 230032, China"},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei 230032, China"},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei 230032, China"},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Long","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei 230032, China"},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Wei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei 230032, China"},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei 230032, China"},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, China"},{"name":"Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People\u2019s Republic of China, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"124337","DOI":"10.1016\/j.jhazmat.2020.124337","article-title":"Land-use change caused by anthropogenic activities increase fluoride and arsenic pollution in groundwater and human health risk","volume":"406","author":"Li","year":"2021","journal-title":"J. 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