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Derived from the placenta, trophoblast cells express nuclear and membrane-bound receptors. Among these receptors is the epidermal growth factor receptor (EGFR) which plays a key role in placental development. Activation of EGFR-mediated signaling in trophoblast cells regulates critical processes, such as proliferation, differentiation, invasion, and fusion during pregnancy, making it essential for normal placental formation. Dysfunction of EGFR in placental trophoblast cells has been associated with adverse pregnancy outcomes, including intrauterine growth restriction, preeclampsia, and preterm birth. Ubiquitous environmental chemicals, like polycyclic aromatic hydrocarbons, polychlorinated biphenyls, organochlorine pesticides, and bisphenols, have been reported to modulate EGFR signaling pathways, potentially contributing to placental dysfunction. This review explores the pivotal role of EGFR signaling in placental development and function, with a focus on how environmental chemicals interfere with EGFR-mediated pathways and placental cell functions as well as their implications for pregnancy outcomes. Findings presented herein underscore the need for further research into the effects of exposure to environmental chemicals on modulating EGFR signaling pathways in the context of placental health.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaf024","type":"journal-article","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T14:17:56Z","timestamp":1740233876000},"page":"11-27","source":"Crossref","is-referenced-by-count":4,"title":["Epidermal growth factor receptor in placental health and disease: pathways, dysfunction, and chemical disruption"],"prefix":"10.1093","volume":"205","author":[{"given":"Anita A","family":"Waye","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Illinois at Chicago , Chicago, IL 60612,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Moeller","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Illinois at Chicago , Chicago, IL 60612,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0308-7231","authenticated-orcid":false,"given":"Almudena","family":"Veiga-Lopez","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Illinois at Chicago , Chicago, IL 60612,","place":["United States"]},{"name":"The Chicago Center for Health and Environment, University of Illinois at Chicago , Chicago, IL 60612,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,22]]},"reference":[{"key":"2025042903522785100_kfaf024-B1","doi-asserted-by":"crossref","first-page":"3946320221092918","DOI":"10.1177\/03946320221092918","article-title":"Bisphenol-A\/radiation mediated inflammatory response activates EGFR\/KRAS\/ERK1\/2 signaling pathway leads to lung carcinogenesis incidence","volume":"36","author":"Abo-Zaid","year":"2022","journal-title":"Int J Immunopathol Pharmacol"},{"key":"2025042903522785100_kfaf024-B2","doi-asserted-by":"crossref","first-page":"107010","DOI":"10.1289\/EHP1539","article-title":"An investigation of the single and combined phthalate metabolite effects on human chorionic gonadotropin expression in placental cells","volume":"125","author":"Adibi","year":"2017","journal-title":"Environ Health Perspect"},{"key":"2025042903522785100_kfaf024-B3","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1093\/biolre\/ioac001","article-title":"The impact of bisphenol A on the placenta","volume":"106","author":"Adu-Gyamfi","year":"2022","journal-title":"Biol Reprod"},{"key":"2025042903522785100_kfaf024-B4","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0960-9822(06)00122-9","article-title":"Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha","volume":"7","author":"Alessi","year":"1997","journal-title":"Curr Biol"},{"key":"2025042903522785100_kfaf024-B5","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.3390\/biom13111616","article-title":"Effects of prenatal exposure to bisphenol A substitutes, bisphenol S and bisphenol F, on offspring\u2019s health: evidence from epidemiological and experimental studies","volume":"13","author":"Algonaiman","year":"2023","journal-title":"Biomolecules"},{"key":"2025042903522785100_kfaf024-B6","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1159\/000243207","article-title":"Epidermal growth factor administered in pregnancy has little effect on placental, fetal and postnatal growth and development in rats","volume":"57","author":"Ali","year":"1990","journal-title":"Biol Neonate"},{"key":"2025042903522785100_kfaf024-B7","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1093\/humrep\/14.2.496","article-title":"Are human placental bed giant cells merely aggregates of small mononuclear trophoblast cells? 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