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.