Maternal exposure to di-(2-ethylhexyl) phthalate disrupts placental growth and development in pregnant mice.
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.
Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.
Teng
T
Zong
Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.
Lidan
L
Lai
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Jia
J
Hu
Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.
Meijun
M
Guo
Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.
Mo
M
Li
Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.
Lu
L
Zhang
Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.
Chengxue
C
Zhong
Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.
Bei
B
Yang
Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.
Lei
L
Wu
Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.
Dalei
D
Zhang
Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.
Min
M
Tang
Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China. Electronic address: kuanghaibin@ncu.edu.cn.
Haibin
H
Kuang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects; D020964:Embryo Loss / Q000139:chemically induced; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018811:Maternal Exposure / Q000009:adverse effects*; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy
D004785:Environmental Pollutants; D004051:Diethylhexyl Phthalate
DEHP; Mouse; Placenta; Pregnancy; Toxicity