Prenatal Polychlorinated Biphenyl Mixture Exposure and Neural Tube Defects: Integrated Epidemiological and Experimental Evidence Implicating Pyroptosis - PubMed
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- #Neural Tube Defects
- #Polychlorinated Biphenyls
- #Pyroptosis
- Prenatal exposure to polychlorinated biphenyl (PCB) mixtures is associated with an increased risk of neural tube defects (NTDs) in humans and mice.
- Specific congeners PCB-52 and PCB-118, as well as total PCBs, were identified as major contributors to elevated NTD risk in epidemiological studies.
- Mouse models dosed with human-relevant PCB mixtures during neurulation showed dose-dependent induction of fetal NTDs, with activation of pyroptosis as a key teratogenic mechanism.
- Multiomics and targeted assays revealed activation of the NLRP3-caspase-1-GSDMD axis and increased IL-18, along with pyroptotic ultrastructural changes, explaining the mechanistic pathway.
- Indoor air pollution is suggested as a potential source of prenatal PCB exposure, and folic acid supplementation may help reduce PCB-associated NTD risk.
- The study presents a framework for real-world mixture risk assessment applicable to birth defect research, integrating epidemiology, in vivo toxicology, and multiomics approaches.