南方医科大学学报

南方医科大学学报 ›› 2016, Vol. 36 ›› Issue (04): 467-.

• • 上一篇    下一篇

妊娠期邻苯二甲酸二（2-乙基）己酯暴露对小鼠胎盘生长发育的影响

张璐，张腾令，宗滕，陈艺璐，任敏，俞晓春，况海斌   

  • 出版日期:2016-04-20 发布日期:2016-04-20

Effect of di-(2-ethylhexyl) phthalate exposure on placental development in pregnant mice

  • Online:2016-04-20 Published:2016-04-20

HTML

PDF

1541

摘要： 目的通过妊娠期邻苯二甲酸二（2-乙基）己酯（DEHP）的暴露，在体观察DEHP暴露对小鼠胎盘生长发育、母胎界面uNK 细胞数及血管形成的影响。方法从妊娠第1天起，通过体外强制性灌胃方法，给予不同剂量的DEHP 125、250、500 mg·kg-1·d-1， 于妊娠第13天取子宫、胎盘标本及称重，通过HE染色和免疫组织化学方法，观察其对小鼠胎盘生长发育、母胎界面uNK细胞数 和血管形成的影响。结果（1）与对照组相比，低剂量DEHP125、250 mg·kg-1·d-1对胚胎着床数没有明显影响（P>0.05）。然而，高 剂量组500 mg·kg-1·d-1 DEHP可显著性降低胚胎着床数（P<0.05）。此外，DEHP暴露可导致胎儿流产率明显上升；（2）与对照组 相比（0.0786±0.0143 g），DEHP呈剂量125、250、500 mg·kg-1·d-1依赖性降低胎盘的重量（分别为：0.0637±0.0133、0.0587±0.0176、 0.0524±0.0183 g；P<0.01），且明显降低胎盘的总面积和海绵层滋养层细胞的面积；（3）与对照组相比，DEHP暴露将导致胎儿血 管分支数显著性降低，血管塌陷及闭锁；（4）与对照组相比（105.1±14.2/HP），DEHP暴露呈剂量依赖性抑制uNK细胞数（分别为： 83.2±10.3、60.7±12.4、50.4±14.5/HP；P<0.01）。结论妊娠期DEHP暴露可显著性抑制胎盘的生长发育，其可能是通过影响母胎 界面的血管形成及uNK细胞数。

Abstract: Objective To investigate the effect of di-(2-ethylhexyl) phthalate (DEHP) exposure on the growth and development of placenta, uterine natural killer (uNK) cell number and angiogenesis at the maternal-fetal interface in pregnant mice. Methods From day 1 of pregnancy, pregnant mice were exposed daily to DEHP by oral gavage at 125, 250, or 500 mg/kg for 13 consecutive days. The uterine and placental tissues were then harvested for HE staining and immunohistochemistry to examine the effect of DEHP exposure on the growth and development of the placenta and angiogenesis and uNK cell number at the maternal-fetal interface. Results Compared with the control group, the mice exposed to 500 mg/kg DEHP, but not those exposed to 125 and 250 mg/kg, showed significantly reduced number of embryo implantation (P<0.05). DEHP exposure significantly increased the rate of abortion. DEHP exposure at 125, 250, and 500 mg/kg significantly and dose-dependently lowered the placental weight compared with that in the control group (0.0637±0.0133, 0.0587±0.0176, 0.0524±0.0183 g vs 0.0786± 0.0143 g, respectively; P<0.01), and significantly reduced the total area of the placenta and area of spongiotrophoblasts. DEHP exposure resulted in a significant reduction in the number of fetal vascular branches, and collapse and atresia of blood vessels. The mice exposed to DEHP at 125, 250, and 500 mg/kg had significantly lowered numbers of uNK cells (83.2±10.3, 60.7±12.4, and 50.4±14.5/HP, respectively) as compared with the control group (105.1±14.2/HP) at the maternal-fetal interface (P<0.01). Conclusion DEHP exposure significantly affects the growth and development of the placenta in mice possibly by suppressing angiogenesis and reducing uNK cell number at the maternal-fetal interface during pregnancy.