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Polystyrene nanoplastics disrupt ovarian development via cytoskeletal remodeling and epigenetic reprogramming particularly in granulosa cells
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Researchers used single-cell RNA sequencing to map polystyrene nanoplastic toxicity in mouse ovaries, identifying granulosa cells as the primary target and showing that 100 nm particles trigger F-actin cytoskeletal remodeling, STAT1-driven epigenetic reprogramming, and necroptosis, disrupting follicle development and hormone production.
Emerging environmental health issues posed by micro- and nanoplastics (M/NPs) have raised significant concerns. Accumulating evidence suggested that M/NPs 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 micro- and nanoplastics (PS-M/NPs, 100 nm and 5 µm) on ovarian development and function in pubertal female mice. Following 35-day exposure, we observed size-dependent reproductive toxicity, with 100 nm PS-NPs causing reduced body weight gain and ovarian size, disrupted folliculogenesis, and altered hormone levels. Leveraging single-cell RNA-sequencing (scRNA-seq), we uncovered profound alterations in intracellular communication networks across seven ovarian cell types. Granulosa cells (GCs) were identified as the primary target of PS-NPs, exhibiting marked transcriptional changes, including dysregulation of FSCN1, a critical actin cytoskeleton regulator. In vitro experiments confirmed that only 100 nm PS-NPs were internalized by GCs, leading to cell cycle arrest, necroptosis, and hormonal dysfunction. Mechanistically, PS-NPs triggered F-actin cytoskeleton remodeling, increasing cell stiffness and histone modifications (H3K4me3, H3K27ac) associated with chromatin accessibility. Integrated ATAC-seq and RNA-seq analyses implicated STAT1 as a key transcriptional regulator driving PS-NP-induced epigenetic and transcriptional changes. Overall, our findings establish the first single-cell resolution atlas of PS-NP-mediated ovarian toxicity, revealing that NPs disrupt reproduction through cytoskeletal damage and epigenetic reprogramming. This work provides unprecedented insights into the molecular and epigenetic consequences of M/NPs in mammalian reproduction, emphasizing the potential health risks of environmental M/NP exposure.
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Polystyrene nanoplastics induce apoptosis, autophagy, and steroidogenesis disruption in granulosa cells to reduce oocyte quality and fertility by inhibiting the PI3K/AKT pathway in female mice
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Researchers found that polystyrene nanoplastics (tiny plastic particles under 1 micrometer) impair egg cell quality in female mice by damaging the ovarian support cells that help eggs mature, triggering cell death and disrupting hormone production. These findings raise important questions about the potential reproductive risks of nanoplastic exposure in women.
The ovarian-related effects of polystyrene nanoplastics on human ovarian granulosa cells and female mice
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This study tested the effects of polystyrene nanoplastics on both human ovarian cells in the lab and on female mice. The nanoplastics accumulated in ovarian tissue, caused cell death, disrupted hormone levels, and reduced egg quality and fertility in mice. These findings suggest that nanoplastic exposure could threaten female reproductive health by damaging the ovaries.
Effects of polystyrene nanoplastics on the female reproductive system in mice: Implications for ovarian function and follicular development
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Researchers exposed female mice to polystyrene nanoplastics orally for 29 days and examined the effects on their reproductive systems. They found that nanoplastic exposure disrupted estrous cycles, impaired follicle development, and altered hormone levels in a dose-dependent manner. The study suggests that nanoplastics, due to their extremely small size, may cross biological barriers and accumulate in reproductive tissues, raising concerns about potential effects on fertility.
Toxicity of polystyrene nanoparticles for mouse ovary and cultured human granulosa cells
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Researchers investigated the effects of polystyrene nanoparticles on female reproductive health using both mouse ovaries and human granulosa cell cultures. They found that nanoparticle exposure damaged ovarian tissue, reduced egg quality, and triggered cell death through oxidative stress and inflammation pathways. The study suggests that nanoplastic exposure may pose risks to female fertility, though more research is needed to confirm effects at real-world exposure levels.
Polystyrene nanoplastics induce ovarian granulosa cell senescence via autophagy suppression
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Researchers found that polystyrene nanoplastics induce premature cellular aging (senescence) in human ovarian granulosa cells by suppressing autophagy, triggering inflammatory signaling and mitochondrial dysfunction, and that restoring autophagy with rapamycin reversed these effects — pointing to a potential mechanism linking nanoplastic exposure to accelerated ovarian aging.
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