Perinatal exposure to di-(2-ethylhexyl) phthalate affects anxiety- and depression-like behaviors in mice

Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disrupter. The present study investigated the effect of DEHP on emotional behavior of mice following perinatal exposure (10, 50, and 200 mg kg(-1) d(-1)) from gestation day 7 through postnatal day 21. The results showed that, in pubertal males (6-w-old), DEHP decreased the time spent in the open arms and the number of entries into them in elevated plus maze and decreased the time in the mirrored chamber and in the light-box; in pubertal females, DEHP decreased the time spent in the open arms and the number of entries into them, suggesting that DEHP exposure made a anxiogenic effect in pubertal offspring regardless of sex. While DEHP effect on anxiety of adult (12-w-old) displayed sex differences, with decreased time spent in the open arms in the adult females. Perinatal exposure to DEPH significantly extended the time of immobility in forced swim task of pubertal offspring and adulthood regardless of sex. Furthermore, DEHP down-regulated the expressions of androgen receptor (AR) in pubertal male hippocampus and of estrogen receptor (ER) β in pubertal female and adult hippocampus of both sexes and inhibited the phosphorylation of ERK1/2 of hippocampus in pubertal mice and adult males. These results suggest that exposure to DEHP early in life affected the anxiety- and depressive-like behaviors of pubertal offspring and even adult. The disruption of gonadal hormones' modulation of behaviors due to down-regulation of AR or ERβ in the hippocampus may be associated with the aggravated anxiety- and depression-like status induced by DEHP.