鼻内滴注空气污染物体内暴露模型的综合分析揭示了胎盘内细胞类型特异性的反应。
Integrated analysis of an in vivo model of intra-nasal exposure to instilled air pollutants reveals cell-type specific responses in the placenta.
机构信息
Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Vienna, Austria.
出版信息
Sci Rep. 2022 May 19;12(1):8438. doi: 10.1038/s41598-022-12340-z.
The placenta is a heterogeneous organ whose development involves complex interactions of trophoblasts with decidual, vascular, and immune cells at the fetal-maternal interface. It maintains a critical balance between maternal and fetal homeostasis. Placental dysfunction can lead to adverse pregnancy outcomes including intra-uterine growth restriction, pre-eclampsia, or pre-term birth. Exposure to environmental pollutants contributes to the development of placental abnormalities, with poorly understood molecular underpinning. Here we used a mouse (C57BL/6) model of environmental pollutant exposure by administration of a particulate matter (SRM1649b at 300 μg/day/mouse) suspension intra-nasally beginning 2 months before conception and during gestation, in comparison to saline-exposed controls. Placental transcriptomes, at day 19 of gestation, were determined using bulk RNA-seq from whole placentas of exposed (n = 4) and control (n = 4) animals and scRNAseq of three distinct placental layers, followed by flow cytometry analysis of the placental immune cell landscape. Our results indicate a reduction in vascular placental cells, especially cells responsible for structural integrity, and increase in trophoblast proliferation in animals exposed to particulate matter. Pollution-induced inflammation was also evident, especially in the decidual layer. These data indicate that environmental exposure to air pollutants triggers changes in the placental cellular composition, mediating adverse pregnancy outcomes.
胎盘是一种异质器官,其发育涉及滋养细胞与胎儿-母体界面的蜕膜、血管和免疫细胞之间的复杂相互作用。它在母体和胎儿内环境之间维持着关键的平衡。胎盘功能障碍可导致不良的妊娠结局,包括宫内生长受限、子痫前期或早产。环境污染物的暴露会导致胎盘异常的发生,其分子基础尚不清楚。在这里,我们使用了一种通过鼻腔内给予颗粒物(SRM1649b 每天 300μg/只)悬浮液的方法,在受孕前 2 个月和妊娠期开始时,在小鼠(C57BL/6)中建立了环境污染物暴露模型,与生理盐水暴露的对照组进行了比较。在妊娠第 19 天,通过对暴露组(n=4)和对照组(n=4)动物的整个胎盘进行批量 RNA-seq 以及对三个不同的胎盘层进行 scRNAseq,随后对胎盘免疫细胞景观进行流式细胞术分析,确定了胎盘转录组。我们的结果表明,暴露于颗粒物的动物的血管胎盘细胞减少,特别是负责结构完整性的细胞,而滋养细胞增殖增加。污染引起的炎症也很明显,尤其是在蜕膜层。这些数据表明,环境暴露于空气污染物会引发胎盘细胞组成的变化,从而导致不良的妊娠结局。