Diethylphthalate, Possible Interactions in Fetal Brain Development

Abstract

Many natural and synthetic compounds, including a variety of the chemicals used as plasticizers or in the pro- duction of cosmetics and therapeutics, have steroid agonist or antagonist activities, altering hormone-regulated gene ex- pression. The phthalate (diethylphthalate, extensively used as a plasticizer and in consumer products, are evaluated using the human renal epithelial cell line 293T/17. Emphasis of the study was on genes essential for central nervous system de- velopment or function. Cells were treated with 1, 10 or 100 μM phthalate and gene expression was measured in treated cells, showing significant up- or down-regulation of a large number of genes in treated compared to untreated cells. Of the 19,000 human genes on the DNA array chip utilized, two specific genes, FGD1 and NGPF2, were selected to corroborate mRNA levels using quantitative real time PCR (qrtPCR) data to confirm results obtained from the microarray determina- tions. FGD1 (faciogenital dysplasia) and NGPF2 (neurite growth-promoting factor 2, also called Midkine, MDK), showed a significant, possibly estrogen-synergistic, down-regulation of genes essential for fetal brain development. These studies were designed to provide data on the gene expression-altering capacity of a widely distributed chemical, diethylphthalate (DEP), and to show possible associations between the previously reported widespread presence of DEP and the DEP me- tabolite, MEP, in urine samples from a reference population, the potential for altered gene expression in human cells in vi- tro, and possible neurodevelopmental effects that could be correlated with in utero exposure to DEP.