Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006, China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
J Hazard Mater. 2015 Oct 30;297:25-33. doi: 10.1016/j.jhazmat.2015.04.065. Epub 2015 Apr 24.
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.
邻苯二甲酸二（2-乙基己基）酯（DEHP）用作增塑剂，广泛分布于环境中。DEHP 暴露会减少胚胎着床，增加胚胎丢失，并降低胎儿体重。然而，关于 DEHP 对妊娠期间胎盘形成的影响尚无详细信息。因此，我们的目的是探讨 DEHP 对体内胎盘生长和发育的影响。从妊娠第 1 天（GD）开始，通过灌胃给予小鼠 125、250、500mg/kg/天的 DEHP，直至处死。结果表明，DEHP 处理显著降低了 GD13 时胎盘的重量。组织病理学检查显示，在 DEHP 处理组中，GD9 时胎盘外细胞滋养层明显变小，GD13 时胎盘总面积和海绵滋养层面积明显减少。在 GD13 时，DEHP 处理的胎盘中 Ascl2、Esx1 和 Fosl1mRNA 的表达水平显著降低。DEHP 给药破坏了胎盘的绒毛血管化，并通过激活 caspase-3 和 caspase-8、上调 Bax 和下调 Bcl-2mRNA 和蛋白来抑制胎盘的增殖和诱导凋亡。总之，这些结果表明，暴露于 DEHP 导致的不良妊娠结局，包括低出生体重和妊娠丢失，可能至少部分通过抑制胎盘生长和发育来介导。
