Cigarette smoking is associated with high level of ferroptosis in seminal plasma and affects semen quality
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Updated: Dec 20, 2025

Flow Cytometric Analysis of Biomarkers for Detecting Human Sperm Functional Defects
Published on: April 21, 2022
Zhanhui Ou1, Qirong Wen2, Yu Deng1
1Center of Reproductive Medicine, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623, Guangzhou, Guangdong, P.R. China.
Purpose:
The effects of cigarette smoking on male semen quality are controversial, and the molecular mechanisms underlying how cigarette smoking affects semen quality are not clear yet.
Methods:
In this study, semen samples from 70 heavy smokers and 75 non-smokers receiving infertility treatment were included. Basic semen parameters in non-smokers and heavy smokers were evaluated. Levels of glutathione (GSH), lipid reactive oxygen species (ROS), iron and GSH-dependent peroxidase 4 (GPX4) protein level were observed in human seminal plasma and in GC-2Spd cells exposed to cigarette smoke condensate (CSC).
Results:
Heavy smokers had significantly higher abnormalities (sperm viability and sperm progressive motility) than non-smoking counterparts. Comparing non-smokers group, GSH level was reduced in the group of heavy smokers (P < 0.05). However, the level of lipid ROS and iron were significantly increased (P < 0.05). Besides, GSH level was reduced following treatment with CSC for 24 h, while lipid ROS and iron levels were increased (P < 0.05). However, the levels were reduced after being co-cultured with Ferrostatin-1 (Fer-1) (P < 0.05). The level of GPX4 protein was reduced after being treated with CSC in 24 h, and increased after being co-cultured with Fer-1(P < 0.05).
Conclusion:
Cigarette smoking is associated with high level of ferroptosis in seminal plasma and affect semen quality.
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