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Maternal exposure to polystyrene nanoplastics triggers ovarian injury in mice offspring: Ferroptosis mediated by the HIF-1α/HO-1 pathway

Original title: Maternal exposure to polystyrene nanoplastics triggers ovarian injury in mice offspring: Ferroptosis mediated by the HIF-1α/HO-1 pathway

Reproductive Toxicology 2026
Qinfeng Sun, Qiao Li, Yijing He, Qianqian Yang, Hui Liu, Wenzhe Yang, Miaoyu Chen, Zhiyi Kong, Weihan Wang, Shiqiang Ju

Summary

Tiny plastic particles (nanoplastics) may be quietly harming future generations' fertility: in a mouse study, pregnant mice exposed to these plastics passed on damage to their offspring's ovaries, disrupting egg-containing follicles and hormone production. The culprit appears to be a form of cell death triggered by iron buildup, and scientists found drugs that could block this damage—offering hope for future treatments. While this research was done in mice, not humans, it raises concerns given how widespread nanoplastic contamination already is in our food, water, and environment.

Polymers
Body Systems
Models
Study Type In vivo

The escalating environmental contamination by nanoplastics (NPs) poses potential risks to reproductive health, yet the intergenerational effects of maternal NPs exposure on offspring ovarian function remain poorly understood. In the current study, pregnant mice were orally administered polystyrene nanoplastics (PS-NPs) throughout gestation, resulting in impaired offspring growth and marked ovarian damage characterized by follicular structural disruption and steroidogenic dysfunction. Transcriptomic profiling of offspring ovaries revealed significant alterations in genes associated with follicle development, oxidative stress, lipid metabolism, and iron ion binding, with pathway analysis identifying ferroptosis and HIF-1 signaling as key affected pathways. Subsequent in vivo and in vitro validation demonstrated that PS-NPs triggered iron accumulation, lipid peroxidation (LPO), and dysregulation of ferroptosis-related proteins (ACSL4, FTH1, SLC7a11, and GPX4) in ovarian granulosa cells. Notably, PS-NPs activated the HIF-1α/HO-1 axis, and pharmacological inhibition of either ferroptosis by Ferrostatin-1 (Fer-1) or HIF-1α by LW6 effectively rescued cellular viability, restored hormone synthesis, and attenuated molecular markers of ferroptosis. Collectively, these findings demonstrate that maternal PS-NPs exposure induces ovarian dysfunction in offspring through HIF-1α/HO-1-mediated-ferroptosis, providing novel insight into the intergenerational toxicity of environmental NPs while identifying potential therapeutic targets for intervention.

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