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Published on: January 7, 2013
Rapamycin inhibits acrolein-induced apoptosis by alleviating ROS-driven mitochondrial dysfunction in male germ cells
1College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Key Lab for Animal Biotechnology of Agriculture Ministry of China, Northwest A&F University, Yangling, 712100, Shaanxi, China.
Objectives:
Acrolein (Acr) is a highly reactive α, β-unsaturated aldehyde, which can induce reactive oxygen species (ROS) generation. Several factors, including lipid peroxidation, clinical use of cyclophosphamide, fried foods, automobile exhausts, smoking and aging can increase its concentration in blood serum. Mounting evidence has suggested that Acr-induced ROS might reduce quality of sperm. Thus, the aim of this study was to examine reproductive toxicity of Acr-caused ROS in vitro and find a means to alleviate it.
Materials And Methods:
We investigated the effects of Acr on male germ cell (MGC)-derived GC-1 cells in vitro. Dihydroethidium and DCFH-DA fluorescent dyes were used to determine generation of intracellular ROS.
Results:
We found that Acr induced ROS generation, which was accompanied by reduced Bcl2/Bax ratio, substantial decline in mitochondrial membrane potential, and further promoted apoptosis of MGCs. Furthermore, Rapamycin was capable of alleviating Acr-induced ROS, reducing ROS-induced apoptosis by increasing ratio of Bcl2/Bax mRNA and proteins, and protecting MGC mitochondrial membranes.
Conclusion:
Rapamycin inhibited Acr-induced apoptosis by alleviating ROS-driven mitochondrial dysfunction in MGCs.
Insights
Acrolein exposure increases reactive oxygen species (ROS) and damages male germ cells. Rapamycin treatment alleviates this damage by reducing ROS and protecting mitochondria, suggesting a therapeutic potential for male reproductive toxicity.
Area of Science:
- Toxicology
- Reproductive Biology
- Biochemistry
Background:
- Acrolein (Acr) is a reactive aldehyde that generates reactive oxygen species (ROS).
- Elevated Acr levels are linked to factors like smoking, aging, and environmental pollutants.
- Acr-induced ROS may negatively impact sperm quality and male fertility.
Purpose of the Study:
- To investigate the reproductive toxicity of Acr-induced ROS in male germ cells (MGCs) in vitro.
- To explore Rapamycin as a potential agent to mitigate Acr-induced reproductive damage.
Main Methods:
- Exposure of MGC-derived GC-1 cells to Acr in vitro.
- Measurement of intracellular ROS using dihydroethidium and DCFH-DA fluorescent dyes.
- Assessment of mitochondrial membrane potential and apoptosis markers (Bcl2/Bax ratio).
Main Results:
- Acr exposure significantly increased ROS generation in MGCs.
- Acr reduced the Bcl2/Bax ratio, decreased mitochondrial membrane potential, and induced apoptosis.
- Rapamycin treatment effectively alleviated Acr-induced ROS and apoptosis, preserving mitochondrial function.
Conclusions:
- Rapamycin mitigates Acr-induced apoptosis in MGCs.
- The protective effect of Rapamycin involves alleviating ROS-driven mitochondrial dysfunction.
- Rapamycin shows promise in counteracting Acr's negative impact on male reproductive cells.

