Prenatal Polychlorinated Biphenyl Mixture Exposure and Neural Tube Defects: Integrated Epidemiological and...

Area of Science:

• Environmental Health
• Toxicology
• Developmental Biology

Background:

• Polychlorinated biphenyls (PCBs) are persistent organic pollutants with known reproductive and developmental toxicity.
• The impact of real-world PCB mixtures on neural tube defect (NTD) risk remains unclear.
• Understanding PCB toxicity mechanisms is crucial for public health and risk assessment.

Purpose of the Study:

• To evaluate the association between prenatal PCB mixture exposure and NTD risk.
• To investigate the underlying biological mechanisms of PCB-induced NTDs.
• To develop a framework for assessing risks from complex environmental chemical mixtures.

Main Methods:

• A case-control study (n=482) estimated prenatal PCB exposure using placental concentrations of 13 congeners.
• In vivo toxicological studies in mice exposed to human-relevant PCB mixtures during neurulation.
• Multiomics analyses (genomics, proteomics, metabolomics) and targeted assays to identify molecular pathways.

Main Results:

• Higher placental PCB levels, particularly PCB-52 and PCB-118, were associated with increased NTD risk.
• Mice exposed to PCB mixtures exhibited dose-dependent NTDs.
• Multiomics data revealed activation of pyroptosis, specifically the NLRP3-caspase-1-GSDMD pathway, suggesting a teratogenic mechanism.

Conclusions:

• Prenatal exposure to PCB mixtures is linked to a higher risk of NTDs.
• Pyroptosis activation is a potential mechanism driving PCB-induced teratogenicity.
• Findings suggest indoor air pollution as a potential exposure source and folic acid as a possible protective measure against PCB-associated NTDs.