Project description:Human ingestion of microplastics (MPs) is common and inevitable due to the widespread contamination of food items, but implications on the gastric digestion of food proteins are still unknown. In this study, the interaction between pepsin and polystyrene (PS) MPs was uncovered by investigating its effect on enzyme activity and conformation while in a simulated human gastric environment. The impact on food digestion was also determined by monitoring the kinetics of protein hydrolysis through static in vitro gastric digestion of cow’s milk contaminated with PS. The binding of pepsin to PS showed that surface chemistry of MPs dictates binding affinity. The key contributor to pepsin adsorption seems to be π−π interactions between the aromatic residues and the PS phenyl rings. During quick exposure (10 minutes) of pepsin to increasing concentrations (222, 2219, 22188 particles/mL) of 10 μm PS (PS10) and 100 μm PS (PS100), total enzymatic activities were not affected remarkably. However, upon prolonged exposure at 1 and 2 hours, preferential binding of pepsin to the small, low zeta-potential PS caused structural changes in the protein which led to a significant reduction of its activity. Digestion of cow’s milk mixed with PS10 resulted in transient accumulation of larger peptides (10-35 kDa) and reduced bioavailability of short peptides (2-9 kDa) in the gastric phase. This, however, was only observed at extremely high PS10 concentration (0.3 mg/mL or 5.46E+05 particles/mL). The digestion of milk peptides, bound preferentially over pepsin on the hard corona around PS10, was delayed up to 15 minutes in comparison to bulk protein digestion. Intact caseins, otherwise rapidly digested, remained bound to PS10 in hard corona for up to 15 minutes. This work presents valuable insights regarding the interaction of MPs, food proteins, and pepsin, and their dynamics during gastric digestion which provides new knowledge and understanding on the potential risks of MPs to human health.

Project description:The emerging environmental health issue posed by micro (nano) plastics (MNPs) has raised significant concerns. Accumulating evidence suggested that MNPs can bioaccumulate in gonads and impair fertility in animals, yet the underlying cellular mechanisms and tissue-specific responses remain poorly understood. In this study, we employed in vivo and in vitro models to systematically investigate the impact of polystyrene microplastics (PS-MPs; 100 nm and 5 µm) on ovarian development and function in pubertal female mice. Following 35 days of exposure, we observed size-dependent reproductive toxicity, with 100 nm PS-MPs causing reduced body weight gain and ovarian size, and compromised ovarian structures and functions, including altered follicle and corpora lutea counts, alongside disrupted hormone levels. Leveraging single-cell RNA-sequencing (scRNA-seq), we uncovered profound alterations in intracellular communication networks and signaling flow patterns across seven identified ovarian cell types. Granulosa cells (GCs) were identified as the primary target PS-MPs, exhibiting marked transcriptional changes, including dysregulation of FSCN1, a critical actin cytoskeleton regulator. In vitro experiments confirmed that only 100 nm PS-MPs were internalized by GCs, leading to cell cycle arrest, necroptosis and hormonal dysfunction. Mechanistically, PS-MPs triggered F-actin cytoskeleton remodeling, increasing cell stiffness and reducing histone marks (H3K4me3, H3K27ac) associated with chromatin accessibility. Integrated ATAC-seq and RNA-seq analyses implicated STAT1 as a key transcriptional regulator driving PS-MP-induced epigenetic and transcriptional changes. Overall, this study first revealed PS-MP-mediated reproductive toxicity from a single-cell perspective, identifying granulosa cells as particularly vulnerable targets. It uncovered novel mechanisms involving cytoskeletal disruption and epigenetic reprogramming, while demonstrating size-dependent internalization patterns that directly correlate with reproductive impairment. These findings provide unprecedented insights into the molecular and epigenetic consequences of MNPs in mammalian reproduction, emphasizing the potential health risks of environmental MNPs exposure.

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Transcriptomic Changes in Human Pulmonary Fibroblasts Following Microplastics Exposure

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