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  3. Gestational exposure to carbon black nanoparticles triggered fetal growth restriction in mice: The mediation of inactivating autophagy-lysosomal degradation system in placental ferroptosis

Gestational exposure to carbon black nanoparticles triggered fetal growth restriction in mice: The mediation of inactivating autophagy-lysosomal degradation system in placental ferroptosis

  • Sci Total Environ. 2025 Jan 10:959:178167. doi: 10.1016/j.scitotenv.2024.178167.
Jing Li 1,  Hongying Gao 2,  Zehua Xu 3,  Biling Gao 2,  Liang Zhang 4,  Bowen Su 2,  Shijing Yang 2,  Jiangling Liu 2,  Ya Liu 2,  Xiuxiu Wang 5,  Heng Wang 6,  Yi Lin 7,  Heqing Shen 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China. Electronic address: leejing@stu.xmu.edu.cn.
  • 2 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China.
  • 3 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China. Electronic address: 32620211150853@stu.xmu.edu.cn.
  • 4 Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361102, China.
  • 5 College of the Environment and Ecology, Xiamen University, Xiamen 361102, China.
  • 6 Zhoushan Municipal Center for Disease Control and Prevention, Zhoushan, Zhejiang 316021, China.
  • 7 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China. Electronic address: tjlinyi@xmu.edu.cn.
  • 8 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China; Department of Obstetrics, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen 361003, China. Electronic address: hqshen@xmu.edu.cn.
PMID: 39721551 DOI: 10.1016/j.scitotenv.2024.178167
Abstract

Carbon black nanoparticles (CBNPs) are ubiquitous in our daily ambient environment, either resulting from tobacco combustion or constituting the core of PM2.5. Despite the potential risk of trafficking CBNPs to the fetus, the underlying toxicity of nano-sized carbon black particles in the placenta remains unambiguous. Pregnant C57BL/6 mice received intratracheal instillation of 30 nm or 120 nm CBNPs. CBNPs deposited in the lungs could infiltrate the red blood cells, further cross into the placenta, and cause fetal growth restriction. Mechanistically, we proposed a two-hit hypothesis in placenta response to CBNPs. The first hit was that CBNPs caused mitochondrial damage, reflected in the reduced mitochondrial matrix, the excessive mitochondrial fission, and the decreased mitochondrial membrane potential and mtDNA copy number. The second hit was that CBNPs disrupted the autophagy-lysosomal degradation system, impeding the removal of dysfunctional mitochondria and resulting in Ferroptosis. Ferrestatin-1, a Ferroptosis inhibitor, and rapamycin, an Autophagy promotor, reversed Ferroptosis and further confirm our suspicion. The findings suggested that CBNPs-triggered double-hit evoked placental Ferroptosis, leading to fetal growth restriction. The study raised concerns about the potential placental toxicity of CBNPs and its impact on the fetal adverse outcome, which may propose potential targets for interventions in placental damage.

Keywords

Autophagy; Carbon black nanoparticles; Ferroptosis; Fetal growth restriction; Mitochondria; Placenta.

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