Critical period for adverse effects on development of reproductive system in male offspring of rats given di- n-butyl phthalate during late pregnancy

Abstract

The objective of this study was to determine the susceptible days for the adverse effects of di- n-butyl phthalate (DBP) on development of reproductive system in male offspring following maternal administration on successive 3-day period during late pregnancy. Pregnant rats were given DBP by gastric intubation at 1000 or 1500 mg/kg on days 12–14 or 18–20 of pregnancy or at 500, 1000 or 1500 mg/kg on days 15–17 of pregnancy. A significant decrease in the maternal body weight gain and/or food consumption was found in the DBP-treated groups regardless of the days on which DBP at 1000 and 1500 mg/kg was given. A significant increase in the number of resorptions per litter was found in the groups given DBP at 1500 mg/kg on days 12–14 and 15–17 of pregnancy. The weights of male and female fetuses were significantly decreased in the groups given DBP at 1000 and 1500 mg/kg on days 12–14 and 18–20 and at 1500 mg/kg on days 15–17. A significant increase in the incidence of fetuses with undescended testes was found at 1500 mg/kg on days 12–14 and at all doses on days 15–17. A significant decrease in the anogenital distance (AGD) of male fetuses was observed in the groups treated with DBP regardless of the days of treatment. The AGD/body weight ratio in male fetuses was significantly reduced in the groups given DBP on days 15–17, but neither on days 12–14 nor 18–20. The AGD of female fetuses in the DBP-treated groups was comparable to that in the control group. It was concluded that period of days 15–17 of pregnancy was the most susceptible for DBP-induced undescended testes and decreased AGD in male offspring.