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Updated: Jul 14, 2026
Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Polystyrene microplastics impaired the function of leydig cells via GRP78/PERK/CHOP mediated endoplasmic reticulum
Qing Zhao1, Lingling Zhai2, Yangyang Song1
1Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016,China.
Abstract:
The toxic effect of Polystyrene Microplastics (PS-MPs) on leydig cells were found in male mice, but the toxic mechanism was not clear. The PS-MPs exposure mice model and cell model were established in this study to explore the leydig cells toxic mechanism. In vivo study, the leydig cells toxicity in male mice was evaluated exposed to PS-MPs for 28 days. And found that the sperm density, mobility and testosterone (T) level decreased, and the sperm malformation rate and malondialdehyde level increased. PS-MPs exposure impaired the function of male reproduction. The results also showed that the levels of testosterone-producing proteins (StAR, P450scc,3β-HSD and CYP17A1) decreased, apoptosis signaling pathways (Bax/Bcl-2, Caspase-8 and Caspase-12) were activated and endoplasmic reticulum stress (GRP78/p-PERK/CHOP) occurred in male mice exposed to PS-MPs. In vitro study, TM3 cells (leydig cells) were treated with 50, 100 and 200 μg/mL of PS-MPs for 24 h. And we found that PS-MPs exposure reduced the cell viability and the level of T, increased reactive oxygen species (ROS) level in TM3 cells. PS-MPs exposure impaired the function of the leydig cells. Further testing revealed that PS-MPs could activate GRP78/p-PERK/CHOP pathway, aggrandized endoplasmic reticulum stress in the leydig cells, then increased apoptosis level, and induced testosterone synthase protein reduction. These could be reversed when exposed to ROS inhibitor or endoplasmic reticulum stress inhibitor. In conclusion, PS-MPs exposure induced the high level of ROS, activated the GRP78/p-PERK/CHOP signaling pathway, enhanced endoplasmic reticulum stress in leydig cells, then apoptosis level increased, which impaired the leydig cell function.
Insights
Polystyrene microplastics (PS-MPs) harm male reproductive health by reducing sperm quality and testosterone. PS-MPs induce oxidative stress and endoplasmic reticulum stress, leading to leydig cell apoptosis and dysfunction.
Area of Science:
- Environmental Toxicology
- Reproductive Biology
- Cellular Stress Mechanisms
Background:
- Polystyrene microplastics (PS-MPs) are environmental contaminants with potential toxic effects.
- The specific mechanisms by which PS-MPs impact leydig cells, crucial for testosterone production, remain unclear.
Purpose of the Study:
- To investigate the toxic mechanisms of PS-MPs on leydig cells in male mice.
- To elucidate the role of oxidative stress and endoplasmic reticulum stress in PS-MPs-induced reproductive toxicity.
Main Methods:
- Established in vivo (male mice) and in vitro (TM3 leydig cells) models for PS-MPs exposure.
- Evaluated sperm parameters, testosterone levels, protein expression, apoptosis markers, reactive oxygen species (ROS), and endoplasmic reticulum stress markers.
Main Results:
- PS-MPs exposure in vivo decreased sperm density, motility, and testosterone levels, while increasing malformations and oxidative stress markers.
- In vitro, PS-MPs reduced leydig cell viability, testosterone production, and increased ROS.
- PS-MPs activated the GRP78/p-PERK/CHOP pathway, inducing endoplasmic reticulum stress and apoptosis, which were reversible with ROS and ER stress inhibitors.
Conclusions:
- PS-MPs exposure impairs male reproductive function through oxidative stress and endoplasmic reticulum stress in leydig cells.
- The GRP78/p-PERK/CHOP signaling pathway is a key mediator of PS-MPs toxicity, leading to apoptosis and reduced testosterone synthesis.
- Inhibiting ROS and endoplasmic reticulum stress can mitigate PS-MPs-induced leydig cell damage.
