1. Academic Validation
  2. Polystyrene Nanoplastics Activate Autophagy and Suppress Trophoblast Cell Migration/Invasion and Migrasome Formation to Induce Miscarriage

Polystyrene Nanoplastics Activate Autophagy and Suppress Trophoblast Cell Migration/Invasion and Migrasome Formation to Induce Miscarriage

  • ACS Nano. 2024 Jan 30;18(4):3733-3751. doi: 10.1021/acsnano.3c11734.
Shukun Wan 1 2 Xiaoqing Wang 1 2 Weina Chen 1 2 Zhongyan Xu 1 Jingsong Zhao 1 Wenxin Huang 1 Manli Wang 1 Huidong Zhang 1
Affiliations

Affiliations

  • 1 Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China.
  • 2 Key Laboratory of Environment and Female Reproductive Health, West China School of Public Health & West China Fourth Hospital, Sichuan University, Chengdu 610041, China.
Abstract

Nanoplastics (NPs), as emerging pollutants, have attracted global attention. Nevertheless, the adverse effects of NPs on female reproductive health, especially unexplained miscarriage, are poorly understood. Defects of trophoblast cell migration and invasion are associated with miscarriage. Migrasomes were identified as cellular organelles with largely unidentified functions. Whether NPs might affect migration, invasion, and migrasome formation and induce miscarriage has been completely unexplored. In this study, we selected polystyrene nanoplastics (PS-NPs, 50 nm) as a model of plastic particles and treated human trophoblast cells and pregnant mice with PS-NPs at doses near the actual environmental exposure doses of plastic particles in humans. We found that exposure to PS-NPs induced a pregnant mouse miscarriage. PS-NPs suppressed ROCK1-mediated migration/invasion and migrasome formation. SOX2 was identified as the transcription factor of ROCK1. PS-NPs activated Autophagy and promoted the Autophagy degradation of SOX2, thus suppressing SOX2-mediated ROCK1 transcription. Supplementing with murine SOX2 or ROCK1 could efficiently rescue migration/invasion and migrasome formation and alleviate miscarriage. Analysis of the protein levels of SOX2, ROCK1, TSPAN4, NDST1, p62, and LC-3BII/I in PS-NP-exposed trophoblast cells, villous tissues of unexplained miscarriage patients, and placental tissues of PS-NP-exposed mice gave consistent results. Collectively, this study revealed the reproductive toxicity of nanoplastics and their potential regulatory mechanism, indicating that NP exposure is a risk factor for female reproductive health.

Keywords

autophagy; migrasomes; migration/invasion; miscarriage; polystyrene nanoplastics; trophoblast.

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