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Evidence indicates that environmental exposures perturb immune regulatory networks, particularly during development, when transcriptional programs governing hematopoiesis, immune cell differentiation, and inflammatory signaling are highly dynamic and sensitive to external stressors. Volatile organic compounds represent an important but incompletely understood source of immunological perturbation. Among these, benzene is a ubiquitous environmental contaminant associated with hematotoxicity and immune dysregulation; however, transcriptional responses to environmentally relevant low-level exposures during development remain poorly characterized. To determine whether benzene exposure engages conserved cross-species immune regulatory pathways, we performed a comparative transcriptomic analysis integrating developmental tissues from 3 vertebrate systems: human placenta, murine placenta, and zebrafish larvae. Bulk RNA sequencing datasets were analyzed to identify transcriptional responses associated with benzene exposure in experimental models (\u22645\u2009ppm) and with benzene adduct levels in maternal plasma for human samples. Because placental gene expression exhibits strong sexual dimorphism, murine datasets were stratified by fetal sex. Pathway- and network-level analyses were used to identify conserved biological responses. We observed a striking convergence on activation of innate immune pathways associated with neutrophil degranulation, IL-8 signaling, and Rho GTPase-mediated inflammatory responses. Further, network analyses identified CXCL8 and ERK1\/2 as shared regulatory hubs linking transcriptional responses across datasets. Together, these findings uncover an evolutionarily conserved innate immune signature associated with benzene exposure during vertebrate development, suggesting that environmental chemical perturbations may disrupt fundamental immune regulatory programs across species.<\/jats:p>","DOI":"10.1093\/toxsci\/kfag085","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:41:39Z","timestamp":1784029299000},"source":"Crossref","is-referenced-by-count":0,"title":["Environmental benzene exposure induces a conserved neutrophil degranulation program across species"],"prefix":"10.1093","volume":"209","author":[{"given":"Jonathan J","family":"Panzer","sequence":"first","affiliation":[{"name":"Department of Public Health Sciences, Henry Ford Health , Detroit, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie L","family":"Connell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Wayne State University , Detroit, MI,","place":["United States"]},{"name":"Institute of Environmental Health Sciences, Wayne State University , Detroit, MI,","place":["United States"]},{"name":"Department of Environmental & Global Health, University of Florida , Gainesville, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Singh","sequence":"additional","affiliation":[{"name":"C.S. 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Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University , Detroit, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M","family":"Stemmer","sequence":"additional","affiliation":[{"name":"Institute of Environmental Health Sciences, Wayne State University , Detroit, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Leydet","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Henry Ford Health , Detroit, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Akemann","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Wayne State University , Detroit, MI,","place":["United States"]},{"name":"Institute of Environmental Health Sciences, Wayne State University , Detroit, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Homegnon Antonin","family":"Ferreol Bah","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Henry Ford Health , Detroit, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Henry Ford Health , Detroit, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea E","family":"Cassidy-Bushrow","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Henry Ford Health , Detroit, MI,","place":["United States"]},{"name":"Henry Ford Health + Michigan State University Health Sciences, Michigan State University , Detroit, MI,","place":["United States"]},{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University , East Lansing, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Ding","sequence":"additional","affiliation":[{"name":"C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University , Detroit, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer K","family":"Straughen","sequence":"additional","affiliation":[{"name":"Henry Ford Health + Michigan State University Health Sciences, Michigan State University , Detroit, MI,","place":["United States"]},{"name":"Department of Women\u2019s Health Services, Henry Ford Health , Detroit, MI,","place":["United States"]},{"name":"Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University , East Lansing, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5057-4155","authenticated-orcid":false,"given":"Tracie R","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Wayne State University , Detroit, MI,","place":["United States"]},{"name":"Institute of Environmental Health Sciences, Wayne State University , Detroit, MI,","place":["United States"]},{"name":"Department of Environmental & Global Health, University of Florida , Gainesville, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert M","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Henry Ford Health , Detroit, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5499-3912","authenticated-orcid":false,"given":"Gil","family":"Mor","sequence":"additional","affiliation":[{"name":"C.S. 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