Deregulation of the Sod1 and Nd1 genes in mouse fetal oocytes exposed to mono-(2-ethylhexyl) phthalate (MEHP).
Mono-(2-ethylhexyl) phthalate (MEHP) is the active metabolite of the diester (DEHP), a well-known reproductive toxicant. Since, different molecular mechanisms underlying this toxicity are not well understood, the effects of MEHP on cell viability and gene expression were assessed in murine fetal oocytes cultured in vitro. Oocyte survival decreased significantly after a 24h exposure to MEHP and hence, the effects of MEHP on changes in gene expression were analyzed using cDNA libraries and differential screenings. In these assays, the genes that suffered the most severe deregulation corresponded to those encoding Cu-Zn superoxide dismutase (Sod1) and a mitochondrial respiratory chain protein (Nd1). Indeed, functional assays on somatic cells transfected with a Sod1 luciferase reporter construct demonstrated its specific MEHP dose-dependent up-regulation, confirming that the expression of this gene is deregulated in response to MEHP.
Bonilla
Edmundo
E
Department of Cell Proliferation and Development, Centro de Investigaciones Biológicas, (C.S.I.C.), Ramiro de Maeztu 9, 28040 Madrid, Spain.
del Mazo
Jesús
J
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000196:embryology; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation
D004785:Environmental Pollutants; D047908:Intracellular Signaling Peptides and Proteins; C432129:Nd1 protein, mouse; D011506:Proteins; D004051:Diethylhexyl Phthalate; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C016599:mono-(2-ethylhexyl)phthalate