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Updated: Jun 7, 2025
A Seminiferous Tubule Squash Technique for the Cytological Analysis of Spermatogenesis Using the Mouse Model
Published on: February 6, 2018
Selenium protects mouse spermatogonia against ivermectin-induced apoptosis by alleviating endoplasmic reticulum
Daniel Chavez Varias1, Sung-Hwan Moon1, Seung Hee Shin1
1Department of Animal Science and Technology, Chung-Ang University, Anseong-Si, Gyeonggi-Do 17546, Republic of Korea.
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 Ca2+ levels, and intracellular protein aggregation. Increased mitochondria-associated ER membrane (MAM) activity through Glucose-regulated Protein 75 (Grp75) overloads the mitochondria with Ca2+, 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.
Insights
Ivermectin (IVM) causes male reproductive toxicity by inducing endoplasmic reticulum (ER) stress and apoptosis in spermatogonia. Selenium (Se) protects against these toxic effects by restoring cellular homeostasis.
Area of Science:
- Toxicology
- Reproductive Biology
- Cellular Stress Response
Background:
- Ivermectin (IVM) is a broad-spectrum anthelmintic with increasing usage.
- Concerns exist regarding IVM's potential toxicity to non-target organisms.
- Understanding IVM's mechanism of toxicity is crucial for risk assessment.
Purpose of the Study:
- To elucidate the mechanism of IVM-induced male reproductive toxicity.
- To investigate the protective role of selenium (Se) against IVM toxicity.
- To explore the involvement of endoplasmic reticulum (ER) stress in IVM's effects.
Main Methods:
- In vitro study using GC-1 spg cells.
- Dose-dependent analysis of IVM exposure.
- Assessment of oxidative stress, calcium levels, and protein aggregation.
- Evaluation of mitochondria-associated ER membrane (MAM) activity and mitochondrial function.
- Analysis of selenium's effects on cellular homeostasis and gene expression.
Main Results:
- IVM induces oxidative stress, calcium dysregulation, and protein aggregation in a dose-dependent manner.
- Increased MAM activity via Grp75 leads to mitochondrial dysfunction and apoptosis.
- Selenium reverses these toxic effects by maintaining ER and redox homeostasis.
- Specific selenoproteins (Gpx4, Selenov) are upregulated with IVM and Se co-treatment.
Conclusions:
- Toxic doses of IVM induce programmed cell death in spermatogonia via ER stress and redox imbalance.
- Selenium mitigates IVM-induced male reproductive toxicity.
- Findings offer insights for refining toxicity evaluations and protecting male fertility.
