Prenatal exposure to environmentally relevant low-dosage dibutyl phthalate reduces placental efficiency in CD-1 mice

Abstract

Dibutyl phthalate (DBP), a phthalate congener, is widely utilized in consumer products and medication coatings. Women of reproductive age have a significant burden of DBP exposure. Prenatal DBP exposure is associated with adverse pregnancy/fetal outcomes in the offspring. However, the role of fetal sex and the general mechanisms underlying DBP exposure-associated adverse pregnancy outcomes are unclear. We hypothesize that prenatal DBP exposure at an environmentally relevant low dosage adversely affects fetal-placental development and function during pregnancy in a fetal sex-specific manner. Adult female CD-1 mice (8 to 10 wk) were orally treated with vehicle (control) or with environmentally relevant low DBP dosages at 0.1 μg/kg/d (DBP0.1) daily from 30 days before pregnancy through gestational day (GD) 18.5. Dam adiposity was measured noninvasively using the echo-magnetic resonance imaging system. Lipid disposition in fetal labyrinth and maternal decidual area of placentas was examined using Oil Red O staining. DBP0.1 exposure did not significantly affect the body weight and adiposity of nonpregnant adult female mice nor the maternal weight gain pattern and adiposity during pregnancy in adult female mice. DBP0.1 exposure does not affect fetal weight but significantly increases the placental weight at GD18.5 (indicative of decreased placental efficiency) in a fetal sex-specific manner. We further observed that DBP0.1 significantly decreased lipid disposition in fetal labyrinth of female, but not male placentas, whereas it did not affect lipid disposition in maternal decidual. In conclusion, prenatal exposure to environmentally relevant low-dosage DBP adversely impacts the fetal-placental efficiency and lipid disposition in a fetal sex-specific manner.

Keywords: dibutyl phthalate; fetal sex; lipid disposition; placenta; prenatal exposure.