Di-(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and widely dispersed in
the environment. DEHP exposure reduces embryo implantations, increases embryonic loss,
and decreases fetal body weights. However, no detailed information is available about
the effect of DEHP on the placentation during pregnancy. Thus, our aim was to explore
the effect of DEHP on the growth and development of placenta in vivo. Mice were administered
DEHP by gavages at 125, 250, 500 mg/kg/day from gestational days (GD) 1 until sacrifice.
Results showed that DEHP treatment significantly reduced the weight of placenta at
GD 13. Histopathologically, in DEHP-treated group, the ectoplacental cones significantly
became smaller at GD9, and total area of placenta and area of spongiotrophoblast were
significantly reduced at GD 13. Expression levels of Ascl2, Esx1 and Fosl1 mRNA dramatically
decreased in DEHP-treated placenta at GD 13. DEHP administration disrupted labyrinth
vascularization of placentas, and inhibited proliferation and induced apoptosis of
placenta by the activation of caspase-3 and -8, up-regulation of Bax and down-regulation
of Bcl-2 mRNA and protein at GD 13. In conclusion, these results suggest that adverse
pregnancy outcomes including low birth-weight and pregnancy loss exposed to DEHP are
possibly mediated, at least in part, via the suppression of placental growth and development.