Maternal exposure to ZIF-8 derails placental function by inducing trophoblast pyroptosis through neutrophils activation in mice

作者全名：Jiang, Yu; Geng, Yanqing; Gao, Rufei; Chen, Zhuxiu; Chen, Jun; Mu, Xinyi; Zhang, Yan; Yin, Xin; Chen, Xuemei; Li, Fangfang; He, Junlin

作者地址：[Jiang, Yu; Chen, Zhuxiu; Zhang, Yan; Yin, Xin; Chen, Xuemei; Li, Fangfang; He, Junlin] Chongqing Med Univ, Sch Publ Hlth, Chongqing, Peoples R China; [Jiang, Yu; Chen, Zhuxiu; Zhang, Yan; Yin, Xin; Chen, Xuemei; Li, Fangfang; He, Junlin] Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chongqing, Peoples R China; [Chen, Jun] Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China; [He, Junlin] Chongqing Med Univ, 1 Yi Xue Yuan Rd, Chongqing 400016, Peoples R China

通信作者：He, JL (通讯作者)，Chongqing Med Univ, 1 Yi Xue Yuan Rd, Chongqing 400016, Peoples R China.

来源：FOOD AND CHEMICAL TOXICOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001223425400001

JCR分区：Q1

影响因子：3.9

年份：2024

卷号：187

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：ZIF-8; Inflammation; Pyroptosis; Neutrophils; Placenta

摘要：Adverse environmental factors during maternal gestation pose a threat to pregnancy. Environmental factors, particularly nanoparticles, can impact pregnancy by causing damage to the placenta. Compared to early gestation, foetuses in late gestation are more robustly developed and at lower risk of adverse effects from environmental factors. Delivery systems for targeted therapy during pregnancy is predominantly focused on their application in late gestation. Zeolitic imidazolate framework-8 (ZIF-8) holds great potential for targeted drug therapy. To evaluate the value of ZIF-8 in targeted treatment of disorders associated with late gestation, it is crucial to investigate the biological effects of ZIF-8 exposure during late gestation. Here, a mouse model exposed to ZIF-8 particles at different doses (5, 10, and 15 mg/kg) during late gestation was constructed. We found that ZIF-8 particles were deposited in the uterus of pregnant mice. ZIF-8 could trigger placental neutrophil aggregation and induce inflammation, which led to trophoblast pyroptosis and impair placental function, adversely affecting the foetus. Neutrophil depletion alleviated placental and foetal damage induced by ZIF-8. This study provides a novel mechanistic view of the reproductive toxicity induced by ZIF-8 and may offer clues to reduce the latent harm of adverse environmental factors to pregnancy.

基金机构：Key project of science and technology research program of Chongqing Municipal Education Commission, China [KJZD-K202000403]; Special Professorship Project of Chongqing Medical University, China [2021-215]

基金资助正文：This work was supported by the [key project of science and technology research program of Chongqing Municipal Education Commission, China] under Grant [KJZD-K202000403] ; and [the Special Professorship Project of Chongqing Medical University, China] under Grant [2021-215] .