Work

Selenium protects mouse spermatogonia against ivermectin-induced apoptosis by alleviating endoplasmic reticulum stress in vitro

Year: 2024

Type: article

Abstract: Ivermectin (IVM) is a widely used anthelmintic in human and veterinary medicine. However, the increasing use of IVM raises concerns about its potential harm against non-targeted organisms. This study demonstrates a novel mechanism where IVM triggers apoptosis via endoplasmic reticulum (ER) stress in GC-1 spg in vitro . The inhibitory effects of selenium (Se) against the toxicological mechanism were also explored. IVM dose-dependently induces oxidative stress, dysregulated Ca 2+ levels, and intracellular protein aggregation. Increased mitochondria-associated ER membrane (MAM) activity through Glucose-regulated Protein 75 (Grp75) overloads the mitochondria with Ca 2+ , causing mitochondrial dysfunction. These simultaneous stressors lead to unfolded protein response and apoptosis. Se reverses all these subcellular events by promoting the expression of selenoprotein-encoding genes to maintain the ER and redox homeostasis. The testis-enriched Glutathione Peroxidase 4 ( Gpx4 ) and the testis-specific Selenoprotein V ( Selenov ) are only upregulated in the IVM and Se co-treatment group, suggesting their potential role in stress response. These findings confirm that toxic doses of IVM lead to programmed cell death in type B spermatogonia through redox imbalance-associated ER stress. This study provides valuable insights into refining male reproductive toxicity evaluation, targeting of ER stress to protect male germ cells, and maintaining male fertility from IVM-induced toxicity. • Ivermectin rapidly causes ER stress-associated apoptosis in mouse spermatogonia. • Se mitigates ivermectin-induced injuries in mouse spermatogonia. • Se activates testis Selenov and Gpx4 only in stressed spermatogonia. • Se protects spermatogonia from ivermectin toxicity by increased selenoproteins.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2024.117307

Authors: Daniel Chavez Varias, Sung-Hwan Moon, Seung Hee Shin, Buom-Yong Ryu

Institution: Chung-Ang University

Language: English

Topic: Endoplasmic Reticulum Stress and Disease

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,990