The Toxicologist - Society of Toxicology

1066 IN UTERO EXPOSURE TO DIBUTYL PHTHALATE
ALTERS GENE EXPRESSION LEVELS IN THE FETAL
RAT FORESKIN.
J. Pike, S. McCahan and K. Johnson. Nemours Biomedical Research, Alfred I.
duPont Hospital for Children, Newark, DE.
Fetal phthalate exposure during a critical window of rat development has been
shown to result in improper formation of the male reproductive system, including
the phallus, through disruption of testosterone production. Gene expression analysis
of the foreskin could provide a translational biomarker correlating with fetal phthalate
exposure and subsequent adverse effects. Fetal rats exposed daily to 100 or
500mg/kg of the endocrine disruptor dibutyl phthalate (DBP) from gestational day
(GD) 16-20 were sacrificed on GD20. Significant decreases in fetal anogenital distance
(AGD) and testis testosterone levels confirmed endocrine disruption at the
500mg/kg DBP exposure level, but not the 100mg/kg level. A significant increase
in the presence of multinucleated germ cells (MNGs) was observed at both exposure
levels. Global gene expression was assessed in male foreskin total RNA with
Illumina RatRef-12 Expression BeadChips. Differentially expressed genes were
identified using LIMMA statistical analysis with a false discovery rate (FDR) adjustment
(p