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High Concentration of Iron Ions Contributes to Ferroptosis-Mediated Testis Injury

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Abstract

In order to explore the effect of excessive iron supplementation on ferroptosis in mouse testes, Kunming mice received injections of varying concentrations of iron. The organ weight, sperm density, and malformation rate were measured. Observations of pathological and ultrastructural alterations in spermatogenic tubules were conducted using haematoxylin eosin (HE) staining and transmission electron microscopy(TEM). Transcript levels of related genes and serum biochemical indicators were measured in mouse testicular tissue. The results showed that higher iron concentration inhibited the growth of mice; reduced the organ coefficients of the testis, heart, and liver; and increased the rate of sperm malformation and mortality. Supplementation with high levels of iron ions can adversely affect the male reproductive system by reducing sperm count, damaging the structure of the seminiferous tubules and causing sperm cell abnormalities. In addition, the iron levels also affected the immune response and blood coagulation ability by affecting the red blood cells, white blood cells and platelets. The results showed that iron ions can affect mouse testicular tissue and induce ferroptosis by altering the expression of ferroptosis-related genes. However, the degree of effect was different for the different concentrations of iron ions. The study also revealed the potential role of deferoxamine in inhibiting the occurrence of ferroptosis. Nevertheless, the damage caused to the testis by deferoxamine supplementation suggests the need for further research in this direction. This study provides reference for reproductive toxicity induced by environmental iron exposure and clarifies the mechanism of reproductive toxicity caused by iron overload and the important role of iron in the male reproductive system.

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Data Availability

The datasets generated during and/or analysed during the current study are not publicly available due to projects involving confidentiality but are available from the corresponding author on reasonable request.

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Funding

This work was supported by grants from the Natural Science Foundation of Henan Province of China (232300421270), the National Natural Science Foundation of China (31960692), the Key Science and Technology Project of Zhumadian City (ZMDSZDZX2023007), 2022 Guiding Plan for Key Scientific Research Projects of Colleges and Universities in Henan Province (22B230008), Commercial Research Funds (2021411701000072; 2021411701000126), and Major Science and Technology Projects in Henan Province (191110110600).

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  1. Chaoying Liu and Ye Wang contributed to the work equally and should be regarded as co-first authors.

Authors and Affiliations

  1. School of Biological and Food Processing Engineering, Huanghuai University, Zhumadian, 463000, Henan Province, China

    Chaoying Liu, Ye Wang, Huili Xia, Yingying Liu, Xinfeng Yang, Xiongyan Yuan, Jiahui Chen, Mingcheng Wang & Enzhong Li

  2. Zhumadian Academy of Industry Innovation and Development, Zhumadian, 463000, Henan Province, China

    Chaoying Liu

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Contributions

Chaoying Liu, Ye Wang and Huili Xia wrote the main manuscript text. Xinfeng Yang, Xiongyan Yuan and Jiahui Chen prepared Figs. 1, 2 and 3. Mingcheng Wang and Yingying Liu prepared Figs. 4, 5, 6, 7 and 8, All authors reviewed the manuscript.

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Correspondence to Enzhong Li.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Huanghuai University.

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Liu, C., Wang, Y., Xia, H. et al. High Concentration of Iron Ions Contributes to Ferroptosis-Mediated Testis Injury. Biol Trace Elem Res (2024). https://doi.org/10.1007/s12011-024-04192-7

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