2. Academic Validation
  3. Gestational exposure to PM2.5 disrupts fetal development by suppressing placental trophoblast syncytialization via progranulin/mTOR signaling

Gestational exposure to PM2.5 disrupts fetal development by suppressing placental trophoblast syncytialization via progranulin/mTOR signaling

  • Sci Total Environ. 2024 Feb 21:921:171101. doi: 10.1016/j.scitotenv.2024.171101.
Yirun Wang 1,  Zhuan Chen 1,  Jie Li 1,  Teng Wan 1,  Renjie Hu 1,  Lu Zhang 1,  Li Qin 1,  Lu Zang 1,  Weijia Gu 1,  Rucheng Chen 1,  Cuiqing Liu 2,  Ran Li 3
Affiliations

Affiliations

  • 1 School of Public Health, Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Zhejiang Chinese Medical University, Hangzhou, China.
  • 2 School of Public Health, Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Zhejiang Chinese Medical University, Hangzhou, China. Electronic address: liucuiqing@zcmu.edu.cn.
  • 3 School of Public Health, Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Zhejiang Chinese Medical University, Hangzhou, China. Electronic address: ranli@zcmu.edu.cn.
PMID: 38387595 DOI: 10.1016/j.scitotenv.2024.171101
Abstract

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.

Keywords

Fine particulate matter; Gestational exposure; Placenta; Progranulin.

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