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Reduction of SLC7A11 and GPX4 Contributing to Ferroptosis in Sperm from Asthenozoospermia Individuals

  • Male Reproduction: Original Article
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Abstract

Ferroptosis is a newly defined form of regulated cell death, which is involved in various pathophysiological conditions. However, the role of ferroptosis in male infertility remains unclear. In this study, 42 asthenozoospermic and 45 normozoospermic individuals participated. To investigate the ferroptosis level in the two groups, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and iron were measured, and mitochondrial membrane potential (MMP) was detected as an indicator of mitochondrial injuries. Compared with the normozoospermic group, ROS (p < 0.05), MDA (p < 0.001), and iron (p < 0.001) of the asthenozoospermic group were significantly increased. However, the asthenozoospermia group had a decreased MMP level (p < 0.05). In addition, the expression levels of GSH-dependent peroxidase 4 (GPX4) (p < 0.001) and solute carrier family 7 member 11 (SLC7A11) (p < 0.05) were also reduced in asthenozoospermic individuals. In asthenozoospermic samples, a significantly high positive correlation was observed between GPX4 mRNA levels and progressive motility (r = 0.397, p = 0.009) and total motility (r = 0.389, p = 0.011), while a negative correlation was observed between GPX4 and iron concentration (r =  − 0.276, p = 0.077). The function of ferroptosis in asthenozoospermic males has never been studied before. In our study, we concluded that GPX4 and SLC7A11 expression levels in asthenozoospermia patients were related to increased ferroptosis and impaired sperm function, revealing novel molecular insights into the complex systems involved in male infertility.

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Author notes

  1. Xiaoling Hao and Hong Wang contributed equally to this work and should be regarded as co-first authors.

Authors and Affiliations

  1. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Xiaoling Hao, Zihan Yang, Liu Ye, Run Huang & Jiangping Meng

  2. Key Laboratory of Diagnostic Medicine Designated By the Ministry of Education, Chongqing Medical University, Chongqing, China

    Xiaoling Hao, Hong Wang & Zihan Yang

  3. School of Laboratory Medicine, Chongqing Medical University, Chongqing, China

    Hong Wang

  4. Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Fang Cui

  5. Sichuan Provincial Maternity and Child Health Care Hospital, No. 290, Shayan West Second Street, Wuhou District, Chengdu City, Sichuan Province, China

    Zihan Yang

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  1. Xiaoling Hao
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Contributions

All authors contributed to the study conception and design. JPM designed this study; XLH and HW performed the experiments and statistical analysis and drafted the manuscript; LY and RH collected the semen samples; FC and ZHY collected the data.

Corresponding author

Correspondence to Jiangping Meng.

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Ethics approval was obtained from the First Affiliated Hospital of Chongqing Medical University’s Ethics Committee (2021–266) for all study techniques.

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The written informed consent was obtained from all the subjects enrolled in this study.

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Not applicable.

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The authors declare no competing interests.

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Hao, X., Wang, H., Cui, F. et al. Reduction of SLC7A11 and GPX4 Contributing to Ferroptosis in Sperm from Asthenozoospermia Individuals. Reprod. Sci. 30, 247–257 (2023). https://doi.org/10.1007/s43032-022-01004-y

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