title: Effects of the organophosphate insecticides phosmet and chlorpyrifos on trophoblast JEG-3 cell death, proliferation and inflammatory molecule production.
abstract: Epidemiological data have associated environmental organophosphate insecticide (OP) exposure during pregnancy with fetal growth deficits. To better understand OP injury that may adversely affect pregnancy, we used the JEG-3 choriocarcinoma cell line, which provide a recognized in vitro model to study placental function. The effects of the OP phosmet (Pm) and chlorpyrifos (Cp) on JEG-3 cells viability, proliferation, cell cycle and inflammatory molecule production were evaluated. Both insecticides affected cellular viability in a concentration- and time-dependent manner, inducing apoptosis and decreasing [(3)H]-thymidine incorporation. However, only Pm reduced DNA synthesis independently of cellular death and decreased the cell percentage at the S-phase. Unlike apoptosis, TNFα production varied with the concentration tested, suggesting that other TNFα independent mechanisms might trigger cell death. No induction of the inflammatory molecule nitric oxide was detected. The mRNA levels of pro-inflammatory IL-6, IL-17 and the anti-inflammatory IL-13 cytokines were differentially modulated. These findings show that Pm and Cp generate a specific toxicity signature, altering cell viability and inducing an inflammatory cytokine profile, suggesting that trophoblasts may represent a possible target for OP adverse effects.
authors.affiliation: IDEPA-CONICET, LIBIQUIMA, Departamento de Química, Facultad de Ingeniería, Universidad Nacional del Comahue, Neuquén, Argentina. natanien@hotmail.com
authors.forename: Natalia
authors.initials: N
authors.lastname: Guiñazú
authors.forename: Viviana
authors.initials: V
authors.lastname: Rena
authors.forename: Susana
authors.initials: S
authors.lastname: Genti-Raimondi
authors.forename: Virginia
authors.initials: V
authors.lastname: Rivero
authors.forename: Gladis
authors.initials: G
authors.lastname: Magnarelli
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004390:Chlorpyrifos / Q000008:administration & dosage / Q000633:toxicity*; D002822:Choriocarcinoma / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism; D010706:Phosmet / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014327:Trophoblasts / Q000187:drug effects* / Q000473:pathology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007306:Insecticides; D012333:RNA, Messenger; D009569:Nitric Oxide; D004390:Chlorpyrifos; D010706:Phosmet