Joint neurodevelopmental and behavioral effects of nonylphenol and estradiol on F1 male rats

The purpose of present study is to examine whether gestational exposure of two major environmental endocrine-disrupting chemicals, nonylphenol (NP) and estradiol (E₂), would affect nervous system development of offspring rats and explore the joint effects of NP and E₂. After impregnation, dams were assigned to seven groups. The first and second groups received gavage with NP at dose levels of 50 mg/kg/day (NP-L) and 100 mg/kg/day (NP-H); the third and fourth groups were gavaged with E₂ at dose levels of 10 μg/kg/day (E₂-L) and 20 μg/kg/day (E₂-H); the fifth and sixth groups were gavaged with joint NP and E₂ [NP 50 mg/kg/day + E₂ 10 μg/kg/day (NP–E₂-L) and NP 100 mg/kg/day+E₂ 20 μg/kg/day (NP–E₂-H)] dissolved in groundnut oil; and the seventh group was orally administered with groundnut oil alone (vehicle control; 2 ml/kg/day), respectively, daily from gestational days 9 to 15 (transplacental exposures). Compared to the control, exclusive NP and E₂ treatment groups, joint exposure to NP–E₂-L and NP–E₂-H has both produced a significant decrease in mean litter size and number of live pups per litter in dams; Offspring rats spent more time to perform cliff-drop aversion reflex, surface righting reflex, air righting reflex, auditory startle, and visual placing; In Morris water maze task, an increased escape latency was presented in offspring rats; In step-down avoidance test, offspring rats jointly exposed to NP and E₂ spent more reaction time. Decrease in acetylcholinesterase activity and increase in choline acetyltransferase activity were observed in the hippocampus of offspring rats. Gestational joint exposure to NP and E₂ might induce nervous development impairment of offspring rats. Moreover, additive toxic effects of NP and E₂ on nervous development have been identified among offspring rats as well.