In utero and lactational exposure to diisopentyl phthalate (DiPeP) induces fetal toxicity and antiandrogenic effects in rats

: A previous study has demonstrated exposure of Brazilian pregnant women to Diisopentyl phthalate (DiPeP), which reduces fetal rat testosterone production in a dose-responsive manner. In this study we examined gene expression of steroidogenic proteins in rat fetal testes and investigated the effects of in utero and lactational DiPeP exposure on male rat reproductive development and function. For the prenatal experiment, we orally exposed pregnant Wistar rats to DiPeP or Di-n-butyl phthalate (reference phthalate) at 0, 125, 250, and 500 mg/kg/day from gestation day 14-18 and the fetal testis was evaluated for transcript expression of Star, Cyp11a1, Cyp17a1, Cyp19a1, Insl3, Ar, Esr1, Esr2 and Gper1 by RT-q PCR. DiPeP lowered mRNA levels of key steroidogenic proteins, lending support to the previously reported reductions in fetal testosterone production. DiPeP also lowered fetal testis transcript levels of Insl3 and changed gene expression of some steroid hormones receptors. Signs of fetal toxicity were observed at the highest dose. For the postnatal experiment pregnant rats were exposed orally to vehicle (canola oil) and four DiPeP doses (1, 10, 100 and 300 mg/kg/day) between gestation day 10 and post-natal day 21. DiPeP induced a range of reproductive and antiandrogenic effects that are typical of the rat phthalate syndrome, including reduced anogenital distance at the highest dose, reduced weight of seminal vesicles at 10 mg/kg/day and above, and testicular morphological and functional changes. Together, our results indicate that DiPeP, a compound relevant to the human exposure scenario, is one of the most active antiandrogenic phthalates.