Decabromodiphenyl ethane exposure-mediated mitochondrial dysfunction drives oxeiptosis in placental trophoblasts and induces fetal growth restriction.

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Tác giả: Bingdi Chao, Xinyue Hu, Hongli Liu, Xiyao Liu, Xin Luo, Hongbo Qi, Lujia Sun, Luming Sun, Jie Wang, Lumei Xie, Jiacheng Xu, Niya Zhou

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: England : Journal of environmental management , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 722887

Decabromodiphenyl ethane (DBDPE), a newly emerging brominated flame retardant (BFR), has garnered increasing attention due to its high production volumes and widespread usage, prompting worries about its possible impacts on human well-being. Prior investigations have highlighted the substantial toxicity of DBDPE to the thyroid, liver, and cardiovascular systems, yet its effects on fetal growth and development remain inadequately understood. This investigation aims to elucidate the underlying mechanisms and consequences of DBDPE exposure on fetal growth and development through both in vivo and in vitro models. Pregnant mice were administered DBDPE orally at doses of 0, 0.05, 0.5, and 5 mg/kg bw/day. Results revealed that gestational DBDPE exposure caused placental damage, resulting in fetal growth restriction (FGR). A significant reduction in the phosphorylation level of AIFM1 Ser116 in placental trophoblasts was observed, specifically correlating with the activation of oxeiptosis. Metabolomic and transcriptomic analyses further suggested that DBDPE exposure disrupts the oxidative phosphorylation (OXPHOS) pathway, thereby impairing mitochondrial function. Notably, treatment with MitoQ, a mitochondria-targeted antioxidant, effectively reversed DBDPE-induced oxeiptosis in placental trophoblasts, alleviating the negative effects of DBDPE on placental damage and FGR. Mechanistically, the mitochondrial dysfunction induced by gestational DBDPE exposure initiates oxeiptosis in placental trophoblasts, exacerbating placental injury and ultimately leading to FGR. In summary, this study integrates the roles of environmental pollutants, oxeiptosis, and mitochondrial dysfunction, offering new insights into the toxicological mechanisms by which DBDPE and other emerging pollutants impact fetal growth and development.
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