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环境细颗粒物暴露破坏妊娠期小鼠胎盘自噬和胎儿发育。

Ambient fine particulate matter exposure disrupts placental autophagy and fetal development in gestational mice.

机构信息

School of Public Health, Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Joint China-US Research Center for Environment and Pulmonary Diseases, Zhejiang Chinese Medical University, Hangzhou 310053, China.

Department of Environmental and Occupational health, Hangzhou Center for Disease Control and Prevention, Hangzhou, Zhejiang, China.

出版信息

Ecotoxicol Environ Saf. 2022 Jul 1;239:113680. doi: 10.1016/j.ecoenv.2022.113680. Epub 2022 May 24.

Abstract

Recent studies have shown that some adverse pregnancy outcomes, especially intrauterine growth restriction (IUGR), are associated with gestational exposure to ambient fine particulate matter (PM). However, potential mechanism remains to be elucidated. In the present study, pregnant C57BL/6 mice were randomly assigned to be exposed to either filtered air or ambient PM in the gestation period via a concentrated whole-body exposure system. We found that gestational PM exposure exerted no effect on implantation, preterm delivery, as well as fetal resorption and death. However, in utero fetal exposure to PM showed a significant reduction in body weight and crown-rump length on GD13 and GD18. Meanwhile, maternal blood sinusoid in placenta was markedly reduced along with abnormal expression of placental nutrient transporters and growth hormone in dams exposed to PM. Additional tests showed gestational PM exposure decreased autophagy-related protein levels and inhibited autophagy flux mainly on GD15. Correspondingly, AMPK/mTOR signaling pathway, a critical negative regulator of autophagy, was activated in placenta on GD15 by PM exposure as well. These findings provide evidences that placental developmental disorder caused by autophagy inhibition might be an important mechanism for the growth restriction caused by PM exposure.

摘要

最近的研究表明,一些不良的妊娠结局,特别是宫内生长受限(IUGR),与妊娠期暴露于环境细颗粒物(PM)有关。然而,潜在的机制仍有待阐明。在本研究中,怀孕的 C57BL/6 小鼠通过全身浓缩暴露系统随机分配到妊娠期暴露于过滤空气或环境 PM 中。我们发现,妊娠期 PM 暴露对植入、早产以及胎儿吸收和死亡没有影响。然而,宫内胎儿暴露于 PM 导致 GD13 和 GD18 时体重和头臀长显著降低。同时,暴露于 PM 的母鼠胎盘血液窦明显减少,胎盘营养转运体和生长激素表达异常。进一步的测试表明,妊娠期 PM 暴露降低了自噬相关蛋白水平,并主要在 GD15 时抑制自噬流。相应地,PM 暴露在 GD15 时激活了胎盘 AMPK/mTOR 信号通路,这是自噬的关键负调控因子。这些发现提供了证据,表明自噬抑制引起的胎盘发育障碍可能是 PM 暴露引起生长受限的重要机制。

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