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Phenylalanine metabolism as a key pathway in polystyrene microplastics-induced abnormal macrophage polarization: Implications for fetal growth and development
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New research in mice found that tiny plastic particles (microplastics) can build up in immune cells at the placenta and trigger inflammation that stunts fetal growth. The culprit was a chain reaction involving an amino acid byproduct that damages a protective enzyme, ramping up inflammatory signals — but remarkably, putting the mice on a diet low in that amino acid (phenylalanine, found in many protein-rich foods) reduced the harm. While this study was done in animals, it offers an early clue about how everyday plastic exposure might affect pregnancy, and hints that diet could one day help offset some risks.
Microplastics have been known to possess reproductive toxicity and can contribute to adverse pregnancy outcomes; however, their specific impact on the immune microenvironment at the maternal-fetal interface remains unclear. This study revealed that polystyrene microplastics (PS-MPs) accumulate extensively in macrophages at the maternal-fetal interface and promote their polarization toward a pro-inflammatory phenotype, ultimately leading to fetal growth restriction. Proteomic analysis indicated that microplastic exposure significantly enriched proteins associated with phenylalanine metabolism in macrophages. Further assays demonstrated a marked increase in intracellular phenylpyruvic acid levels, suggesting it as a key effector molecule mediating abnormal macrophage polarization in this process. Mechanistically, phenylpyruvic acid binds to acid ceramidase-1 and accelerates its degradation, which subsequently elevates ceramide levels and activates the MAPK/ATF2/COX2 signaling pathway. This cascade upregulates inflammatory factors, ultimately causing dysregulation of maternal-fetal interface macrophages and impaired fetal development. A phenylalanine-restricted diet significantly alleviated PS-MPs-induced aberrant macrophage polarization and fetal growth restriction. This study revealed the PS-MPs-induced adverse pregnancy outcomes through modulation of immune cell fate for the first time, providing a novel metabolic-immune perspective for understanding pregnancy complications associated with microplastics exposure.
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