biostudies-literatureElkin ERNational Institute of Environmental Health SciencesOffice of the Vice President for Research, Wayne State UniversityNational Institute of Diabetes and Digestive and Kidney DiseasesNIA NIH HHSNIDDK NIH HHSNIEHS NIH HHSNational Institute on Aging1595-1619https://www.ebi.ac.uk/biostudies/studies/S-EPMC7961173biostudies-literatureUnknown95(5)Trichloroethylene (TCE) is an industrial solvent and widespread environmental contaminant. Although TCE exposure is prevalent, epidemiological studies of TCE exposure associations with adverse birth outcomes are inconclusive. Prior studies show that the TCE metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) exhibits toxicity in a placental cell line. In the current study, genome-wide gene expression and gene set enrichment analyses were used to identify novel genes and pathway alterations in the HTR-8/SVneo human trophoblast cell line and human placental villous explants treated with DCVC at concentrations relevant to human exposures. In the cells, concentration- and time-dependent effects were observed, as evidenced by the magnitude of altered gene expression after treatment with 20 µM DCArchives of toxicologyTranscriptional profiling of the response to the trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine revealed activation of the eIF2α/ATF4 integrated stress response in two in vitro placental models.PMC7961173R01 DK107535P30 ES017885R01 ES028802P30 ES020957P42 ES017198T32 DK071212P30 AG053760R01 AG055406R01 ES025531R01 ES025574T32 ES007062Loch-Caruso RBakulski KMColacino JAKilburn BAArmant DRElkin ERBridges DfalseTranscriptional profiling of the response to the trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine revealed activation of the eIF2α/ATF4 integrated stress response in two in vitro placental models.Trichloroethylene (TCE) is an industrial solvent and widespread environmental contaminant. Although TCE exposure is prevalent, epidemiological studies of TCE exposure associations with adverse birth outcomes are inconclusive. Prior studies show that the TCE metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) exhibits toxicity in a placental cell line. In the current study, genome-wide gene expression and gene set enrichment analyses were used to identify novel genes and pathway alterations in the HTR-8/SVneo human trophoblast cell line and human placental villous explants treated with DCVC at concentrations relevant to human exposures. In the cells, concentration- and time-dependent effects were observed, as evidenced by the magnitude of altered gene expression after treatment with 20 µM DC2021-01-01T00:00:00Z2021 May2025-04-04T21:16:23.062Z2025-02-19T03:10:23.449ZS-EPMC79611733372512810.1007/s00204-021-03011-5