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

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. © 2024 Elsevier B.V.