{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T16:08:06Z","timestamp":1789488486920,"version":"build-2803163510"},"reference-count":70,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515030251"],"award-info":[{"award-number":["2024A1515030251"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Innovation and Entrepreneurship Training Program For Undergraduate of Jinan University","award":["CX26412"],"award-info":[{"award-number":["CX26412"]}]},{"name":"the Innovation and Entrepreneurship Training Program For Undergraduate of Jinan University","award":["CX26417"],"award-info":[{"award-number":["CX26417"]}]},{"name":"Key Laboratory of Environmental Toxicology, Anhui Higher Education Institute","award":["2022-AHMUT-KF-2"],"award-info":[{"award-number":["2022-AHMUT-KF-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Organophosphate flame retardants (OPFRs) may affect semen quality, but the mechanisms remain unclear. This study included 157 men from the SEARCH cohort and evaluated the associations between urinary OPFR levels and semen quality, and the role of the seminal plasma metabolome. Overall, bis(2-butoxyethyl) phosphate (BBOEP) was negatively associated with progressive motility (\u03b2 [95% confidence interval (CI)]: \u22120.090 [\u22120.175, \u22120.005]), and some associations between OPFRs and semen quality were more pronounced among men with male-factor infertility. Furthermore, widespread associations were observed between OPFRs and metabolites, as well as between metabolites and semen quality. For example, BBOEP was negatively associated with alkyl-phosphatidylethanolamine (O-PE) (\u03b2 [95% CI] = \u22120.030 [\u22120.058, \u22120.002]), while O-PE exhibited an inverted U-shaped dose\u2013response relationship with progressive motility (P overall = 0.041, P nonlinear = 0.020). The lipid pathway of O-PE \u2192 phosphatidylethanolamine plasmalogen (P-PE) \u2192 plasmalogen phosphatidylcholine (P-PC) was downregulated in men with lower sperm counts (Z-score = \u22122.345, P = 0.019). Adverse outcome pathway (AOP) analysis predicted that OPFR-related reproductive toxicity may be associated with mitochondrial dysfunction, oxidative stress, and apoptosis involving the phospholipase A2 (PLA2) gene family. In conclusion, our findings may provide new clues to the mechanisms underlying the reproductive toxicity of OPFRs.<\/jats:p>","DOI":"10.1021\/acs.est.6c08766","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T01:19:42Z","timestamp":1788398382000},"page":"25344-25357","source":"Crossref","is-referenced-by-count":0,"title":["Seminal\nPlasma Metabolomics Reveals Potential Metabolic\nPathways Linking Organophosphate Flame Retardant Exposure to Impaired\nSemen Quality"],"prefix":"10.1021","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5406-2669","authenticated-orcid":true,"given":"Guangtong","family":"Huang","sequence":"first","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]},{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia-Yuhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Fang","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Tan","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wu","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Zhong","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiehao","family":"Li","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjun","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Pharmaceutical University , , ,","place":["Guangzhou, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Gong","sequence":"additional","affiliation":[{"name":"Guangdong Pharmaceutical University , , ,","place":["Guangzhou, China, 510006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7439-299X","authenticated-orcid":true,"given":"Yongfeng","family":"Deng","sequence":"additional","affiliation":[{"name":"Southeast University , , ,","place":["Nanjing, China, 210009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1186-1300","authenticated-orcid":true,"given":"Yichao","family":"Huang","sequence":"additional","affiliation":[{"name":"Anhui Medical University , , ,","place":["Hefei, China, 230032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Women and Children\u2019s Hospital Chongqing Medical University , , ,","place":["Chongqing, China, 401147"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2001-4923","authenticated-orcid":true,"given":"Pan","family":"Yang","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]},{"name":"Jinan University , , ,","place":["Guangzhou, China, 510632"]},{"name":"Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education , ,","place":["Guangzhou, China, 510632"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"2026091511110525400_cit1","unstructured":"World Health Organization.\n          . 1 in 6 people\nglobally affected by infertility: WHO. https:\/\/www.who.int\/news\/item\/04-04-2023-1-in-6-people-globally-affected-by-infertility. (accessed May 12, 2026)."},{"issue":"1","key":"2026091511110525400_cit2","doi-asserted-by":"publisher","first-page":"111","DOI":"10.24041\/ejmr2020.19","article-title":"Male Infertilityand\nSemen Parameters:Ademystified Review","volume":"7","author":"Wasim","year":"2020","journal-title":"Era\u2019s\nJ. Med. Res."},{"issue":"2","key":"2026091511110525400_cit3","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1093\/humupd\/dmac035","article-title":"Temporal Trends\nin Sperm Count: A Systematic Review and Meta-Regression Analysis of\nSamples Collected Globally in the 20th and 21st Centuries","volume":"29","author":"Levine","year":"2023","journal-title":"Hum. Reprod. Update"},{"issue":"7","key":"2026091511110525400_cit4","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1093\/humrep\/deab124","article-title":"Temporal\nTrends in Semen Concentration and Count among 327 373 Chinese Healthy\nMen from 1981 to 2019: A Systematic Review","volume":"36","author":"Lv","year":"2021","journal-title":"Hum. Reprod."},{"issue":"4","key":"2026091511110525400_cit5","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1111\/andr.12789","article-title":"Effects of Brominated and Organophosphate Ester Flame\nRetardants on Male Reproduction","volume":"8","author":"Hales","year":"2020","journal-title":"Andrology"},{"key":"2026091511110525400_cit6","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1373426","article-title":"Effects of Long and Short Ejaculatory\nAbstinence on Sperm Parameters: A Meta-Analysis of Randomized-Controlled\nTrials","volume":"15","author":"Lo Giudice","year":"2024","journal-title":"Front. Endocrinol."},{"key":"2026091511110525400_cit7","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1255304","article-title":"Effects of Cigarette Smoking on Semen\nQuality, Reproductive Hormone Levels, Metabolic Profile, Zinc and\nSperm DNA Fragmentation in Men: Results from a Population-Based Study","volume":"14","author":"Osadchuk","year":"2023","journal-title":"Front. Endocrinol."},{"issue":"3","key":"2026091511110525400_cit8","doi-asserted-by":"publisher","DOI":"10.3390\/toxics12030195","article-title":"A Review of\nthe Distribution and Health Effect of Organophosphorus\nFlame Retardants in Indoor Environments","volume":"12","author":"Song","year":"2024","journal-title":"Toxics"},{"key":"2026091511110525400_cit9","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.scitotenv.2018.04.320","article-title":"Occurrence, Distribution\nand Risk Assessment of Organophosphate Esters\nin Surface Water and Sediment from a Shallow Freshwater Lake, China","volume":"636","author":"Xing","year":"2018","journal-title":"Sci. Total Environ."},{"key":"2026091511110525400_cit10","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.envpol.2017.12.017","article-title":"Organophosphate\nand Brominated Flame Retardants in Australian Indoor Environments:\nLevels, Sources, and Preliminary Assessment of Human Exposure","volume":"235","author":"He","year":"2018","journal-title":"Environ. Pollut."},{"issue":"9","key":"2026091511110525400_cit11","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.35484","article-title":"Urinary\nConcentrations\nof Organophosphate Flame-Retardant Metabolites in the US Population","volume":"7","author":"Huang","year":"2024","journal-title":"JAMA Network Open"},{"key":"2026091511110525400_cit12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2023.114876","article-title":"Triphenyl\nPhosphate Induced Apoptosis of Mice Testicular Leydig Cells and TM3\nCells through ROS-Mediated Mitochondrial Fusion Inhibition","volume":"256","author":"Wang","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"2026091511110525400_cit13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2024.116003","article-title":"Cresyl Diphenyl Phosphate\nExposure Induces Reproductive Functional\nDefects in Men and Male Mice","volume":"271","author":"Jiang","year":"2024","journal-title":"Ecotoxicol. 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Sci."},{"key":"2026091511110525400_cit20","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2024.1340261","article-title":"Association between\nOrganophosphate Flame Retardant\nExposure and Lipid Metabolism: Data from the 2013\u20132014 National\nHealth and Nutrition Examination Survey","volume":"12","author":"Cheng","year":"2024","journal-title":"Front.\nPublic Health"},{"issue":"2","key":"2026091511110525400_cit21","doi-asserted-by":"publisher","DOI":"10.3390\/metabo14020124","article-title":"Exposure to OPFRs Is\nAssociated with\nObesity and Dysregulated Serum Lipid Profiles: Data from 2017\u20132018\nNHANES","volume":"14","author":"Li","year":"2024","journal-title":"Metabolites"},{"issue":"8","key":"2026091511110525400_cit22","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1093\/humrep\/deaf085","article-title":"Novel Insights\ninto the Lipid Signalling in Human Spermatozoa","volume":"40","author":"Serafini","year":"2025","journal-title":"Hum. 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Endocrinol."},{"issue":"6","key":"2026091511110525400_cit26","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1093\/advances\/nmy057","article-title":"The Effect of Nutrients\nand Dietary Supplements on Sperm Quality Parameters: A Systematic\nReview and Meta-Analysis of Randomized Clinical Trials","volume":"9","author":"Salas-Huetos","year":"2018","journal-title":"Adv. Nutr."},{"issue":"1","key":"2026091511110525400_cit27","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.fertnstert.2014.10.010","article-title":"Dietary Fatty Acid Intakes and Asthenozoospermia: A\nCase-Control Study","volume":"103","author":"Eslamian","year":"2015","journal-title":"Fertil. 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Environ.\nManage."},{"key":"2026091511110525400_cit33","unstructured":"Geneva: World Health Organization.\n          \n          WHO\nLaboratory Manual for the Examination and Processing of Human Semen. 2021."},{"issue":"8","key":"2026091511110525400_cit34","doi-asserted-by":"publisher","first-page":"5031","DOI":"10.1021\/acs.est.9b07180","article-title":"Aluminum Exposure\nand Gestational Diabetes Mellitus:\nAssociations and Potential Mediation by n-6 Polyunsaturated Fatty\nAcids","volume":"54","author":"Huang","year":"2020","journal-title":"Environ. Sci. Technol."},{"key":"2026091511110525400_cit35","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.28022.1","article-title":"BioPAN:\nA Web-Based Tool to Explore Mammalian Lipidome Metabolic Pathways\non LIPID MAPS","volume":"10","author":"Gaud","year":"2021","journal-title":"F1000Research"},{"key":"2026091511110525400_cit36","doi-asserted-by":"publisher","DOI":"10.1016\/j.comtox.2024.100317","article-title":"Revealing an Adverse\nOutcome Pathway Network for Reproductive Toxicity Induced by Atrazine,\nvia Oxidative Stress","volume":"30","author":"Vieira","year":"2024","journal-title":"Comput. Toxicol."},{"key":"2026091511110525400_cit37","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.envpol.2017.11.082","article-title":"Prenatal Urinary\nPolycyclic Aromatic Hydrocarbon Metabolites, Global\nDNA Methylation in Cord Blood, and Birth Outcomes: A Cohort Study\nin China","volume":"234","author":"Yang","year":"2018","journal-title":"Environ. Pollut."},{"key":"2026091511110525400_cit38","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2025.109907","article-title":"Exposure to\nIndividual Organophosphate Esters and Their Mixture in Relation to\nSemen Quality in Chinese Men","volume":"205","author":"Tang","year":"2025","journal-title":"Environ. Int."},{"key":"2026091511110525400_cit39","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.envint.2017.10.001","article-title":"Exposure\nto Organophosphate Flame Retardant Chemicals in the U.S. General Population:\nData from the 2013\u20132014 National Health and Nutrition Examination\nSurvey","volume":"110","author":"Ospina","year":"2018","journal-title":"Environ. 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Saf."},{"key":"2026091511110525400_cit43","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2020.105698","article-title":"Organophosphate Esters and Their\nMetabolites in Paired Human Whole Blood, Serum, and Urine as Biomarkers\nof Exposure","volume":"139","author":"Hou","year":"2020","journal-title":"Environ. Int."},{"key":"2026091511110525400_cit44","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2021.148837","article-title":"A Review on\nOrganophosphate Flame\nRetardants in the Environment: Occurrence, Accumulation, Metabolism\nand Toxicity","volume":"795","author":"Yao","year":"2021","journal-title":"Sci. Total Environ."},{"issue":"1","key":"2026091511110525400_cit45","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.reprotox.2010.08.006","article-title":"Organophosphorous\nPesticide\nExposures and Sperm Quality","volume":"31","author":"Perry","year":"2011","journal-title":"Reprod. 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Health Perspect."},{"issue":"3","key":"2026091511110525400_cit48","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1093\/humupd\/dmn004","article-title":"Oxidative\nStress and Male Infertility\u2500a Clinical Perspective","volume":"14","author":"Tremellen","year":"2008","journal-title":"Hum. Reprod. Update"},{"key":"2026091511110525400_cit49","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2024.108596","article-title":"Bioactivity Assessment\nof Organophosphate Flame Retardants via a Dose-Dependent Yeast Functional\nGenomics Approach","volume":"186","author":"Guan","year":"2024","journal-title":"Environ. 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