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

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

  • J Environ Manage. 2025 Apr:379:124775. doi: 10.1016/j.jenvman.2025.124775.
Lumei Xie 1,  Hongli Liu 1,  Xinyue Hu 1,  Jiacheng Xu 2,  Bingdi Chao 1,  Jie Wang 3,  Lujia Sun 1,  Xiyao Liu 4,  Niya Zhou 3,  Luming Sun 5,  Hongbo Qi 6,  Xin Luo 7
Affiliations

Affiliations

  • 1 Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, 400016, China.
  • 2 Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, 400016, China; Women and Children's Hospital of Chongqing Medical University, Chongqing, 401147, China.
  • 3 Women and Children's Hospital of Chongqing Medical University, Chongqing, 401147, China.
  • 4 State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China; National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, 100191, China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China.
  • 5 Shanghai Key Laboratory of Maternal Fetal Medicine, Department of Fetal Medicine and Prenatal Diagnosis Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204, China.
  • 6 Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, 400016, China. Electronic address: qihongbocy@gmail.com.
  • 7 Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, 400016, China. Electronic address: 14802315@qq.com.
PMID: 40049011 DOI: 10.1016/j.jenvman.2025.124775
Abstract

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.

Keywords

Decabromodiphenyl ethane; Fetal growth restriction; MitoQ; Mitochondrial dysfunction; Oxeiptosis; Trophoblasts.

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