Work

Nanoscale tire wear particles disrupt the blood–testis barrier and impair spermatogenesis through ROS–driven ferritinophagy and ferroptosis

Year: 2026

Type: article

Abstract: Background Tire wear particles (TWPs) are a major source of micro- and nanoplastics. However, reports on nanoscale tire wear particles, especially regarding their potential hazards to the male reproductive system, remain scarce. Results Here, we examined whether nanoscale tire wear particles impair spermatogenesis and blood-testis barrier integrity through oxidative stress-linked ferroptotic injury. Using a 70-day oral exposure model in pubertal male mice and complementary GC-2 and TM4 cell models, we found that high-dose particle exposure reduced epididymal sperm density, increased sperm abnormalities, disrupted seminiferous epithelial organization, and increased BTB permeability. TWPs shifted metabolomic profiles toward lipid and iron dysregulation, suppressed SLC7A11/GPX4, increased ACSL4 and labile Fe²⁺, and depleted junctional proteins. Ferrostatin-1 reduced lipid peroxidation, iron accumulation, cell death, and junctional protein loss, indicating a functional contribution of ferroptosis. Mechanistically, TWPs first induced total and mitochondrial reactive oxygen species and mitochondrial depolarization, which were restrained by N-acetylcysteine. Downstream, autophagic ferritin degradation amplified ferroptotic injury, as chloroquine or NCOA4 knockdown preserved ferritin, reduced malondialdehyde accumulation, restored GPX4/SLC7A11, and improved viability. NCOA4 depletion did not substantially blunt ROS induction, placing ferritinophagy after oxidative stress. Conclusions Together, these data define a ROS-initiated, NCOA4-dependent ferritinophagy-ferroptosis axis that connects nanoscale TWPs to BTB failure and impaired spermatogenic homeostasis. This work provides a mechanistic basis for future assessment of reproductive health risks associated with TWPs exposure.

Source: Journal of Nanobiotechnology

DOI: 10.1186/s12951-026-05106-6

Authors: Wenyang Pang, Yin Cao, Shuang Du, Zuowen Liang, Hongliang Wang, Lingyun Liu

Institutions: Affiliated Hospital of North Sichuan Medical College, First Hospital of Jilin University

Language: English

Topic: Sperm and Testicular Function

Subfield: Reproductive Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,790