2. Academic Validation
  3. Polystyrene nanoplastics induce ovarian granulosa cell senescence via autophagy suppression

Polystyrene nanoplastics induce ovarian granulosa cell senescence via autophagy suppression

  • NanoImpact. 2025 Dec 6:41:100607. doi: 10.1016/j.impact.2025.100607.
Haoyue Hu 1,  Haotong Ouyang 2,  Lien Ma 2,  Qianhan Xu 3,  You Peng 4,  Meng Meng 5,  Tao Zhang 6
Affiliations

Affiliations

  • 1 Reproductive Medicine Center, The Eighth Affiliated Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, Guangdong, China; Department of Obstetrics and Gynecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
  • 2 Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.
  • 3 Department of Obstetrics and Gynecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
  • 4 Department of Gynecology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
  • 5 Department of Fetal Medicine & Prenatal Diagnosis Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: [email protected].
  • 6 Assisted Reproductive Technology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: [email protected].
PMID: 41360355 DOI: 10.1016/j.impact.2025.100607
Abstract

Polystyrene nanoplastics (PS-NPs) pose escalating threats to female reproductive health, yet their impact on ovarian granulosa cell senescence remains poorly understood. This study investigates the mechanisms by which 50 nm PS-NPs induce senescence in human ovarian granulosa KGN cells. Exposure to PS-NPs (50-250 μg/mL) triggered concentration-dependent cellular senescence in KGN cells, as evidenced by increased senescence-associated β-galactosidase (SA-β-gal) activity, suppressed Lamin B1 expression, and enhanced activation of the P53/P16 signaling axis. PS-NPs also triggered both a senescence-associated secretory phenotype (SASP) and senescence-associated mitochondrial dysfunction (SAMD), marked by upregulated pro-inflammatory cytokines (IL-6, IL-8, IL-1β) and increased Reactive Oxygen Species (ROS) levels coupled with mitochondrial membrane potential (ΔΨm) disruption. Mechanistically, we demonstrated that PS-NP-induced senescence in KGN cells is mediated by Autophagy suppression. Autophagy modulation experiments revealed that rapamycin (an Autophagy activator) reversed PS-NP-triggered senescence, SASP and SAMD, whereas 3-methyladenine (3-MA, an Autophagy inhibitor) exacerbated these effects. These results establish Autophagy suppression as a critical mediator of PS-NP-induced granulosa cell senescence and highlight the therapeutic potential of Autophagy enhancement to mitigate PS-NPs-associated reproductive toxicity. Our study provides novel insights into the molecular pathways linking environmental nanoplastics to premature ovarian aging, underscoring the urgent need for strategies to address nanoplastics exposure in reproductive health.

Keywords

Autophagy; Ovarian granulosa cell; Polystyrene nanoplastics; Senescence.

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