bioRxiv Science⌕ Search

bioRxiv · 10.1101/2025.06.27.662011

Polystyrene and polyethylene terephthalate nanoplastics differentially impact mouse ovarian follicle function

Abstract

Exposure to micro- and nanoplastics is unavoidable. Foods and beverages contain plastic particles from environmental contamination and processing and packaging materials, which are frequently made of polyethylene terephthalate (PET). Micro- and nanoplastics have been detected in human tissues such as the brain, liver, and placenta, as well as in ovarian follicular fluid, but little is known about the effects nanoplastics have on the female reproductive system. In addition, few studies on the health impacts of nanoplastics have been performed using environmentally relevant plastic types and concentrations. Thus, this research tested the hypothesis that nanoplastics made of spherical polystyrene (PS), a common model nanoplastic, would have different effects on cultured mouse ovarian follicles compared to secondary PET nanoplastics at environmentally relevant doses. The ovary is a highly sensitive reproductive organ responsible for the development of follicles, which contain the oocyte, and production of steroid hormones. Follicles were harvested from adult mouse ovaries and cultured for 96 h with vehicle, spherical commercially available 200 nm PS nanoplastics (1-100 {micro}g/mL), or lab-generated 240 nm PET nanoplastics (0.1-10 {micro}g/mL). PS and PET nanoplastic exposure inhibited follicle growth and altered expression of genes related to steroid synthesis, cell cycle, and oxidative stress. PET nanoplastics increased levels of pregnenolone and decreased expression of Cyp17a1. Overall, both plastic types altered ovarian function, but they impacted different genes in similar pathways. These findings suggest that nanoplastic exposure at environmentally relevant concentrations may pose a risk to female reproductive health by disrupting hormonal and molecular pathways. In addition, environmentally relevant plastic types and doses are necessary for studying health impacts of nanoplastics. HighlightsO_LINanoplastics disrupted ovarian function in vitro C_LIO_LISecondary PET and virgin PS differently inhibited follicle growth and ovarian gene expression C_LIO_LIPET exposure increased pregnenolone, impacting steroid hormone pathways C_LIO_LIEnvironmentally relevant plastics can harm female reproductive health C_LI

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Alahmadi, H., Nadeem, M., Pujols, A. M., Reynolds, R., Islam, M. S., Gupta, I., Potts, C., Harbolic, A., Lafontant, G., Mitra, S., Warner, G. R.. 2025-07-01. Polystyrene and polyethylene terephthalate nanoplastics differentially impact mouse ovarian follicle function. https://doi.org/10.1101/2025.06.27.662011

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Lipid-ASO therapeutics exhibit differential tissue targeted delivery upon systemic or local CNS administration

Antisense oligonucleotides (ASOs) are a powerful therapeutic modality, but their full potential is hindered by pharmacokinetic properties that affect tissue and cellular delivery. Lipid conjugation is increasingly used to modulate ASO's biodistribution and promote extrahepatic activity, yet lipid dependent effects on in vivo functional delivery, particularly in the central nervous system (CNS), remain less explored. Here, we performed a side by side in vivo comparison of cholesterol, palmitic acid (C16:0), docosanoic acid (C22:0), and eicosapentaenoic acid (C20:5) conjugated to a fully phosphorothioated 3 10 3 LNA gapmer ASO targeting the Malat1 long non coding RNA. Lipid-ASO conjugates were administered systemically or locally in the brain of mice and evaluated for tissue level and cellular level distribution by imaging, qPCR and single-cell RNA sequencing, simultaneously annotating cell origin and global transcriptional changes within the cell. Following systemic administration in mice, lipid conjugation improved overall multi organ efficacy compared to unconjugated ASO, but with pronounced tissue specific differences. Single cell sequencing of liver and heart transcriptomes revealed lipid dependent cellular uptake patterns and transcriptional responses distinct from administration of unconjugated ASO. After intracerebroventricular administration, selected fatty acid conjugates enhanced silencing in deep brain regions such as the striatum, whereas cholesterol conjugation impaired functional delivery despite increased CNS retention. Light-sheet microscopy showed restricted parenchymal penetration of cholesterol ASOs compared with broader but heterogeneous distribution of palmitic acid conjugate. Together, these findings demonstrate that lipid identity critically determines ASO efficacy, productive cellular uptake, and regional CNS engagement, emphasizing the need for context specific lipid design in ASO therapeutic development.

pharmacology and toxicology↗

Novel Dissymmetric Ionizable Lipid-Assembled Lipid Nanoparticles for Delivery of Ferroptosis-Related siRNA in Diabetic Treatment

Small interfering RNA (siRNA) enables precise post-transcriptional gene silencing for refractory diseases, yet its clinical translation remains limited by the lack of safe and efficient delivery vectors. Inspired by the dissymmetric alkyl chain architecture of natural membrane phospholipids, we designed and synthesized 34 novel ionizable lipids with dissymmetric hydrophobic tails and formulated them into lipid nanoparticles (LNPs). Through systematic physicochemical and biological assessments, we established clear structure-activity relationships and identified two lead LNPs (O14-LNP, H18a-LNP) with superior endosomal escape capacity, enhanced in vivo gene silencing potency, and favorable biosafety relative to the clinical benchmark MC3-LNP. In both streptozotocin-induced and spontaneous db/db type 2 diabetes (T2D) mouse models, lead LNPs delivering ferroptosis-related siRNAs effectively ameliorated glucose and lipid metabolic disorders, restored islet function, and alleviated hepatic steatosis. This study not only lays a theoretical foundation for the rational design of novel ionizable lipids, but also validates the therapeutic potential of siRNA therapy targeting ferroptosis, providing a versatile delivery platform and targeted therapeutic strategy for the treatment of T2D.

pharmacology and toxicology↗

Inhibition of Mitochondrial Complex III Causes Dopaminergic Neurodegeneration by Redox Stress in Caenorhabditis elegans

Environmental factors including chemical exposures are important contributors to Parkinsons disease (PD). Nearly all well-validated chemicals involved in PD affect mitochondria, and the great majority of those identified inhibit mitochondrial complex I, causing ATP depletion and oxidative stress. We hypothesized that inhibition of mitochondrial complex III would also cause dopaminergic neurotoxicity. Using Caenorhabditis elegans to evaluate the in vivo effects of complex III-inhibiting pesticides antimycin A and pyraclostrobin, we found that both caused selective dopaminergic neurotoxicity. We evaluated exacerbation of dopaminergic neurotoxicity by the presence of -synuclein, and pdr-1/PRKN and pink-1/PINK1 mutant backgrounds and found increased neurotoxicity for pdr-1. Complex III inhibition caused a more-oxidized cellular environment in those neurons and pharmacological and genetic antioxidant interventions rescued neurotoxicity, but energetic rescue attempts did not. Finally, optogenetic production of superoxide anion specifically at complex III caused dopaminergic neuronal damage. Thus, redox stress at complex III following chemical exposure causes dopaminergic neurotoxicity in vivo in C. elegans.

pharmacology and toxicology↗