Maternal Exposure to PM2.5 Affects Fetal Lung Development at Sensitive Windows.

Maternal Exposure to PM2.5 Affects Fetal Lung Development at Sensitive Windows.
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母亲接触 PM2.5 会影响胎儿肺部敏感窗口的发育。

DOI:
10.1021/acs.est.9b04674
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发表时间:
2019-12
影响因子:
11.4
通讯作者:
Sang Nan
Sang Nan
中科院分区:
环境科学与生态学1区
文献类型:
--
作者:
Yue Huifeng;Ji Xiaotong;Li Guangke;Hu Meng;Sang Nan

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肺的发育从胚胎期持续到成年期。此前的流行病学研究指出,母亲在敏感窗口期接触大气污染物会扰乱肺部发育,增加出生后患肺部疾病的风险,但实验证据不足。在本研究中,我们每隔一天通过口咽抽吸将插头阳性小鼠暴露于 PM2.5(3 毫克/千克体重),旨在测试母体 PM2.5 暴露是否影响后代的产前肺部发育。首先,母体 PM2.5 暴露会降低 E18.5 时的胚胎重量和头臀长度,但在早期发育阶段 (E0-E16.5) 则不会。其次,母体 PM2.5 暴露不会妨碍肺芽和气管的规范化,也不会导致肺发育早期阶段 (E0-E16.5) 的分支形态发生、远端肺上皮和间质分化异常。然而,暴露显着扰乱了肺远端上皮和间质分化,导致气管完整环减少,并抑制了E18.5肺发育相关基因(Nkx2.1、Tbx4、Tbx5和Sox9)的表达。最后,我们发现暴露不仅增加了 PM2.5 结合金属含量(Pb 和 Cu),而且还引起胎盘炎症反应,这种炎症反应从母亲传播给胎儿,导致发育异常。
Lung development continues from the embryonic period to adulthood. Previous epidemiological studies have noted that maternal exposure of atmospheric pollutants during the sensitive windows disturbed the lung development and increased the risk of lung diseases after birth, but the experimental evidence was insufficient. In the present study, we exposed plug-positive mice to PM2.5 (3 mg/kg b.w.) by oropharyngeal aspiration every other day, and intended to test whether maternal PM2.5 exposure affected prenatal lung development in the offspring. First, maternal PM2.5 exposure decreased embryo weight and crown-rump length at E18.5 but not in earlier developmental stages (E0-E16.5). Second, maternal PM2.5 exposure did not prevent lung-bud and tracheal specification, and did not cause abnormalities in branching morphogenesis, distal lung epithelium, and mesenchyme differentiation in earlier stages of lung development (E0-E16.5). However, the exposure significantly disturbed the distal lung epithelium and mesenchyme differentiation of lung, led to reduced intact rings of trachea, and suppressed the expression of lung development-related genes (Nkx2.1, Tbx4, Tbx5, and Sox9) at E18.5. Finally, we found that the exposure not only increased PM2.5-bound metal content (Pb and Cu) but also caused inflammatory response in the placenta, which transmitted from the mother to the fetus and contributed to the developmental abnormalities.
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