滋养层
PI3K/AKT/mTOR通路
胎儿
胎盘
宫内生长受限
怀孕
基因敲除
生物
信号转导
内分泌学
细胞生物学
男科
内科学
医学
细胞培养
遗传学
作者
Yirun Wang,Zhuan Chen,Jie Li,Teng Wan,Renjie Hu,Lu Zhang,Qin Li,Lili Zang,Weijia Gu,Rucheng Chen,Cuiqing Liu,Ran Li
标识
DOI:10.1016/j.scitotenv.2024.171101
摘要
Recent epidemiological and animal studies have indicated that ambient fine particulate matter (PM2.5) exposure during pregnancy is closely associated with intrauterine growth restriction (IUGR). However, the underlying mechanisms remain to be revealed. In this study, we found that gestational exposure to PM2.5 significantly decreased fetal weight and crown-rump length in mice, accompanied by insufficient placental trophoblast syncytialization and increased expression of progranulin (PGRN) in mice placenta. Administering PGRN neutralizing antibody to pregnant mice alleviated growth restriction and insufficient placental trophoblast syncytialization caused by PM2.5, accompanied with suppressed activation of the mTOR signaling pathway. Furthermore, in vitro experiments using human placental BeWo cells showed that 10 μg·mL−1 PM2.5 activated PGRN/mTOR signaling and suppressed forskolin-induced cell fusion, which was blocked by knockdown of PGRN. Taken together, our results demonstrated that PM2.5 exposure during pregnancy inhibited placental trophoblast syncytialization by activating PGRN/mTOR signaling, leading to abnormal placental development and IUGR. This study reveals a novel mechanism underlying the developmental toxicity of PM2.5 exposure during pregnancy.
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