First identification of microplastics in umbilical cord blood and their direct target proteins: A pioneering discovery.

Microplastics (MPs) have been detected in human organs and peripheral blood, but their presence in the fetal circulation and their direct biomolecular interactions remain unknown. This study combined Raman spectroscopy, Py-GC/MS, and SEM to detect and quantify MPs in human umbilical cord blood (UCB), and employed limited proteolysis-coupled mass spectrometry (LiP-MS) to identify direct protein targets. MPs were ubiquitous in all UCB samples (n = 10), with a mean concentration of 41.128 µg/g. Polystyrene (PS), polyethylene (PE), polyvinyl chloride (PVC), and polypropylene (PP) were the predominant polymers. Notably, LiP-MS revealed 84 proteins that directly bound to MPs, with a significant enrichment in proteins involved in the hypoxia-inducible factor (HIF) signaling pathway. Subsequent in vitro experiments demonstrated that MPs suppressed the self-renewal and clonogenic capacity of UCB-derived hematopoietic stem cells (HSCs) in a concentration-dependent manner, concomitant with the inhibition of the HIF pathway. Genetic ablation of HIF-1α abolished the MP-induced suppression, establishing a causal role for this pathway. Our findings provide the first evidence of systemic MP infiltration into the fetal circulation and delineate a direct mechanistic link to impaired hematopoiesis via HIF-1α signaling, highlighting a potential risk for developmental toxicity.