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.

Project description:Micro- and nanoplastics (MNPLs) have emerged as pervasive environmental pollutants, raising growing concerns about their potential health risks. Their documented presence in the human bloodstream highlights the need to understand their interactions with endothelial cells and their role in cardiovascular diseases such as atherosclerosis. However, the full implications of these interactions remain largely unknown. To address this, we investigated the impact of three sizes (30, 50, and 100 nm) of polystyrene carboxylated nanoplastics (PS-C-NPLs) on human umbilical vein endothelial cells (HUVECs) at 100 µg/mL. By integrating in vitro assays with bioinformatic transcriptomic analyses, we employed a multimodal approach to comprehensively investigate the effects of PS-C-NPLs on endothelial cells. In vitro assessments included nanoplastics (NPLs) internalisation (flow cytometry, confocal microscopy, TEM), morphological and internal complexity changes (flow cytometry), genotoxicity (comet assay), and functional alterations, such as cholesterol biosynthesis (Filipin III staining), migration (wound healing assay), angiogenesis, and inflammation (IL-6 ELISA). Additionally, RNA sequencing provided transcriptomic insights into the cellular response to PS-C-NPLs, complementing the in vitro findings and revealing molecular pathways underlying the observed effects. All three PS-C-NPL sizes were rapidly internalised by HUVECs within 20 minutes, inducing significant alterations in cell morphology, internal complexity, and function. PS-C-NPLs caused genotoxic damage and disrupted cholesterol metabolism, migration, angiogenesis, and inflammatory responses. Notably, some effects exhibited a size-dependent trend, with similarities emerging between carboxylated polystyrene (PS-C) 50 and 100 nm NPLs, while the smallest 30 nm NPL showed slightly distinct responses. Transcriptomic analyses reinforced these findings, revealing shared pathways across all three PS-C-NPLs —linked to cholesterol metabolism, endothelial-to-mesenchymal transition, DNA damage, and inflammation — alongside size-specific molecular signatures. This study is the first to comprehensively link transcriptomic changes to size-dependent functional alterations in endothelial cells induced by PS-C-NPLs. Our findings demonstrate that PS-C-NPLs significantly impair endothelial cell function and integrity in a size-dependent manner, underscoring their potential cardiovascular risks.

Dataset Information

Polystyrene microplastics disrupt ovarian development via cytoskeletal remodeling and epigenetic reprogramming particularly in granulosa cells [ATAC-seq]

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets