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Zhanhang Wang¹, Shujuan Liu², Zefang Cheng²

¹College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China; Key Laboratory of Livestock Biology Northwest A&F University, Yangling, Shaanxi 712100, China.

Food Research International (Ottawa, Ont.)

|December 21, 2023

Abstract:

Human and animal exposure to microplastics (MPs) contained in food is inevitable because of their widespread existence in the environment. Nevertheless, MPs toxicity studies in ruminants often lack attention. Here, we assessed the cytotoxicity of polystyrene microplastics (PS MPs) on goat mammary epithelial cells (GMECs). Compared to controls, PS MPs treatment significantly reduced cell viability, altered cell morphology and disrupted organelle integrity. Detection of membrane potential and reactive oxygen species (ROS) suggested that PS MPs induced mitochondrial dysfunction and oxidative stress. Further transcriptome analysis also confirmed alterations in these pathways. In addition, several genes related to endoplasmic reticulum (ER) homeostasis were significantly regulated in the transcriptional profile. Subsequent experiments confirmed that PS MPs induce ER stress via the PERK/eIF2α/CHOP pathway, accompanied by intracellular Ca²⁺ overload. Meanwhile, downstream activation of the Bax/Bcl-2 pathway and caspase cascade released apoptotic signals, which led to apoptosis in GMECs. Interestingly, the addition of PERK inhibitor (ISRIB) attenuated PS MPs-induced ER stress and apoptosis, which suggests that ER stress may exacerbate PS MPs-induced cytotoxicity. This work reveals the impact of MPs on mammalian cytotoxicity, enriches the mechanisms for the toxicity of MPs, and provides insight for further assessment of the risk of MPs in food.

Insights

Polystyrene microplastics (PS MPs) harm goat mammary cells by causing mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum (ER) stress. Inhibiting ER stress reduces PS MP-induced cell damage and apoptosis.

Area of Science:

Environmental Toxicology
Cell Biology
Mammalian Cell Studies

Background:

Microplastic (MP) exposure is ubiquitous in food chains, posing risks to both human and animal health.
Ruminant exposure to MPs and their subsequent toxicity remain understudied.
Polystyrene microplastics (PS MPs) are common environmental contaminants.

Purpose of the Study:

To investigate the cytotoxic effects of PS MPs on goat mammary epithelial cells (GMECs).
To elucidate the molecular mechanisms underlying PS MP-induced cellular damage, including mitochondrial and endoplasmic reticulum (ER) stress.
To assess the role of ER stress in PS MP toxicity.

Main Methods:

Exposure of GMECs to varying concentrations of PS MPs.
Assessment of cell viability, morphology, and organelle integrity.
Mitochondrial membrane potential and reactive oxygen species (ROS) detection.
Transcriptome analysis to identify affected cellular pathways.
Investigation of ER stress markers (PERK/eIF2α/CHOP pathway) and intracellular calcium levels.
Analysis of apoptosis-related pathways (Bax/Bcl-2) and caspase activation.
Treatment with a PERK inhibitor (ISRIB) to evaluate its protective effects.

Main Results:

PS MPs significantly reduced GMEC viability, altered cell morphology, and disrupted organelle integrity.
Mitochondrial dysfunction and oxidative stress were induced by PS MPs.
Transcriptome analysis revealed significant alterations in pathways related to ER homeostasis.
PS MPs triggered ER stress via the PERK/eIF2α/CHOP pathway, leading to intracellular Ca2+ overload.
Apoptosis was induced through the Bax/Bcl-2 pathway and caspase cascade activation.
Inhibition of ER stress using ISRIB attenuated PS MP-induced cytotoxicity and apoptosis.

Conclusions:

PS MPs exhibit significant cytotoxicity towards mammalian cells, specifically GMECs.
ER stress, mitochondrial dysfunction, and oxidative stress are key mechanisms mediating PS MP toxicity.
ER stress exacerbates PS MP-induced cytotoxicity, highlighting its critical role.
This study provides crucial insights into the cellular impacts and toxicological mechanisms of MPs in food.

Read full analysis

Keywords:

Apoptosis Endoplasmic reticulum stress Goat mammary epithelial cells Oxidative stress Polystyrene microplastics Transcriptome

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