Jiang Wenyu, Deng Yu, Song Zifan, Xie Yajuan, Gong Lixin, Chen Yilu, Kuang Haibin
Department of Physiology, Basic Medical College, Nanchang University, Nanchang, China.
Department of Clinic Medicine, School of Queen Mary, Nanchang University, Nanchang, China.
Front Physiol. 2020 Feb 7;11:51. doi: 10.3389/fphys.2020.00051. eCollection 2020.
Perfluorooctanoic acid (PFOA) is a widely used perfluorinated compound and known to cause developmental toxicity which includes the increase of resorbed embryo, decrease of fetal survival, and fetal growth retardation. Nevertheless, whether it is associated with alteration of placental development remains unknown. Pregnant mice were gavaged with 0, 2.5, 5, 10 mg PFOA /kg/day from pregnancy day (PD) 1 to PD 13. Results showed that PFOA exposure markedly decreased the placental weight and caused interstitial edema of placenta. Laminin staining indicated that blood sinusoids area was shrunken in placenta of PFOA-exposed mice. Furthermore, PFOA treatment significantly reduced numbers of uNK cells. Western blot analysis revealed that levels of Bax and cleaved-caspase 3 proteins were markedly up-regulated in PFOA-treated groups. In addition, TEM examination showed that PFOA treatment caused rupture of nuclear membrane and nuclear pyknosis and fragmentation. Thus, our results suggested that gestational PFOA exposure significantly inhibited development of early placenta through shrinkage of labyrinth vessels and downregulation of uNK cells and apoptosis induction, which may result in adverse gestational outcomes.
全氟辛酸（PFOA）是一种广泛使用的全氟化合物，已知会导致发育毒性，包括吸收胚胎增加、胎儿存活率降低和胎儿生长迟缓。然而，它是否与胎盘发育改变有关仍不清楚。从妊娠第1天（PD）到PD 13，给怀孕小鼠灌胃0、2.5、5、10毫克PFOA/千克/天。结果表明，PFOA暴露显著降低了胎盘重量，并导致胎盘间质水肿。层粘连蛋白染色表明，PFOA暴露小鼠胎盘中血窦面积缩小。此外，PFOA处理显著减少了uNK细胞的数量。蛋白质印迹分析显示，PFOA处理组中Bax和裂解的半胱天冬酶3蛋白水平显著上调。此外，透射电镜检查显示，PFOA处理导致核膜破裂、核固缩和核碎裂。因此，我们的结果表明，孕期暴露于PFOA会通过迷路血管收缩、uNK细胞下调和诱导凋亡显著抑制早期胎盘发育，这可能导致不良妊娠结局。
