Pontifex Tasha, Yang Xinran, Tracy Ayna, Craig Zelieann, Zhou Chi
School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ, United States.
Department of Obstetrics and Gynecology, The University of Arizona, Tucson, AZ, United States.
Toxicol Sci. 2025 Apr 12. doi: 10.1093/toxsci/kfaf050.
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 (8-10wks) were orally treated with vehicle (control) or with environmentally relevant low DBP dosages at 0.1 μg/kg/day (DBP0.1) daily from 30 days before pregnancy through gestational day (GD) 18.5. Dam adiposity was measured non-invasively 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 non-pregnant 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, while it did not affect lipid disposition in maternal decidual.
Prenatal exposure to environmentally relevant low-dosage DBP adversely impacts the fetal-placental efficiency and lipid disposition in a fetal sex-specific manner.
邻苯二甲酸二丁酯(DBP)是一种邻苯二甲酸酯同系物,广泛应用于消费品和药物涂层中。育龄妇女面临着显著的DBP暴露负担。产前DBP暴露与后代不良妊娠/胎儿结局相关。然而,胎儿性别所起的作用以及DBP暴露相关不良妊娠结局的一般机制尚不清楚。我们假设,孕期以环境相关低剂量产前暴露于DBP会以胎儿性别特异性方式对孕期胎儿-胎盘的发育和功能产生不利影响。
成年雌性CD-1小鼠(8 - 10周龄)在怀孕前30天至妊娠第18.5天,每天经口给予赋形剂(对照)或环境相关低剂量DBP,剂量为0.1μg/kg/天(DBP0.1)。使用回声磁共振成像系统对母鼠肥胖情况进行无创测量。采用油红O染色检查胎盘胎儿迷路和母体蜕膜区的脂质分布。
DBP0.1暴露对未怀孕成年雌性小鼠的体重和肥胖情况以及成年雌性小鼠孕期的母体体重增加模式和肥胖情况均无显著影响。DBP0.1暴露不影响胎儿体重,但以胎儿性别特异性方式显著增加了妊娠第18.5天的胎盘重量(表明胎盘效率降低)。我们进一步观察到,DBP0.1显著降低了雌性而非雄性胎盘胎儿迷路中的脂质分布,而对母体蜕膜中的脂质分布没有影响。
产前暴露于环境相关低剂量DBP会以胎儿性别特异性方式对胎儿-胎盘效率和脂质分布产生不利影响。