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| Plasticizer DEHP inhibits the growth of mouse spermatogonia GC-1 spg through the ferroptosis pathway#br# |
| LIN Bohan1, LIU Wei1, WANG Zixuan1, WANG Chao1, LI Tao1, YANG Qin2, YU Qiwen1, SUN Xiaochun1#br# |
（1. School of Medicine, Jiangsu University, Zhenjiang Jiangsu 212013； 2. Department of Women′s Health, the Fourth Hospital Affiliated to Jiangsu University, Zhenjiang Jiangsu 212002, China)
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Abstract Objective： To investigate the mechanism of DEHP-induced damage on mouse spermatogonial cell GC-1 spg function. Methods： GC1 spg were treated with various concentrations of DEHP (0, 30, 60, 90, 120 μmol/L). The effects of DEHP on the proliferation and migration of GC-1 spg were observed by CCK8 test, colony formation test and Transwell assay, and the relative contents of iron ion (Fe3+) and malondialdehyde (MDA) in GC-1 spg cells were determined by chemical spectrophotometry. The expression of cystine glutamate reverse transporter (xCT) and glutathione peroxidase 4 (GPX4) in GC1 spg was detected by Western blotting assay. The expression of intracellular reactive oxygen species （ROS） and the changes of mitochondrial membrane potential were detected by cellular immunofluorescence. The proliferation ability of GC-1 spg was detected by CCK8 assay after ferroptosis inhibitor Ferrostatin1 (1 μmol/L) was cotreated with DEHP (90 μmol/L) 24 h. Results： Compared with the control group (0 μmol/L), the proliferation, cloning and migration ability of cells in 30, 60, 90, 120 μmol/L DEHP groups were significantly decreased, while the contents of MDA,ROS and Fe3+ (90, 120 μmol/L DEHP group) were significantly increased. The mitochondrial membrane potential (60, 90, 120 μmol/L DEHP group) and the expression of GPX4 (60, 90, 120 μmol/L DEHP group), xCT protein were significantly decreased. The ability of cell proliferation after co-treatment of DEHP and Ferrostatin-1 was significantly higher than that of DEHP alone. Conclusion： DEHP can inhibit proliferation and migration capacity of GC-1 spg and reduce the expression of GPX4 and xCT proteins in GC-1 spg, possibly causing ferroptosis.
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Received: 10 November 2022
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