Polyethylene terephthalate microplastics impair erectile function through macrophage mediated cGAS-STING ferroptosis

Area of Science:

• Environmental Science
• Toxicology
• Urology

Background:

• Microplastic pollution is a growing global issue.
• The effects of microplastics on male reproductive health, specifically erectile dysfunction (ED), are not well understood.

Purpose of the Study:

• To investigate the impact of chronic polyethylene terephthalate microplastic (PET-MP) exposure on male reproductive health.
• To elucidate the underlying mechanisms linking PET-MP exposure to ED.

Main Methods:

• Assessed PET-MP levels in human corpus cavernosum (CC) tissues from patients with and without ED.
• Utilized a rat model for chronic PET-MP exposure studies.
• Employed cell assays to investigate cellular mechanisms, including macrophage responses and mitochondrial function.

Main Results:

• Higher PET-MP burden observed in CC tissues of patients with ED.
• Chronic PET-MP exposure in rats dose-dependently impaired erectile function, increased fibrosis, and reduced smooth muscle.
• PET-MPs induced macrophage mitochondrial dysfunction, ROS generation, mtDNA release, cGAS-STING activation, and ferroptosis, leading to inflammation and endothelial-to-mesenchymal transition.

Conclusions:

• A cGAS-STING-ferroptosis signaling axis links environmental PET-MP exposure to ED.
• Innate immune responses and ferroptosis pathways are implicated in microplastic-induced male reproductive dysfunction.
• Targeting these pathways presents potential therapeutic strategies for ED caused by microplastic exposure.