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Tanshinone IIA protects mouse testes from heat stress injury by inhibiting apoptosis and TGFβ1/Smad2/Smad3 signaling pathway

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Cell Stress and Chaperones Aims and scope

Abstract

Heat stress can cause testicular damage and affect male fertility. Tanshinone IIA (TSA) is a monomer substance derived from plants, with antioxidant and anti-apoptotic effects. Whether it can repair testicular damage caused by heat stress is unclear. This study aims to construct a mouse testicular heat stress injury model and intervene with TSA. Various methods such as histopathology, high-throughput sequencing, bioinformatics analysis, and molecular biology were used to investigate whether TSA can alleviate heat stress-induced testicular injury and its mechanism. Results showed that heat stress significantly reduced the diameter of the mouse seminiferous tubules, increased cell apoptosis in the testicular tissue, and significantly decreased testosterone levels. After TSA intervention, testicular morphology and cell apoptosis improved significantly, and testosterone secretion function was restored. High-throughput transcriptome sequencing found that key differentially expressed genes between the HS group and the control and TSA groups clustered in the apoptosis and TGFβ signaling pathways. Using western blot technology, we found that the HS group upregulated TGFβ1/Smad2/Smad3 pathway protein expression, causing cell apoptosis, testicular tissue organic lesions, and affecting testicular secretion function. Through TSA intervention, we found that it can inhibit TGFβ1/Smad2/Smad3 pathway protein expression, thereby restoring testicular damage caused by heat stress. This study confirms that TSA can effectively restore testicular damage caused by heat stress in mice, possibly by inhibiting the TGFβ1/Smad2/Smad3 pathway to suppress apoptosis.

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Acknowledgements

This work was supported by the Guangxi natural science foundation of China, under grant numbers 2019JJB14021, 2020GXNSFAA159099; doctoral research start-up fund of Guangxi university of Chinese medicine under grant number 2017BS013, Nanning scientific research and technology development program under grant number 20213024, Nanning Qingxiu district science and technology plan project under grant number 2020024, 2020025, Nanning Jiangnan district science and technology plan project under grant number 202001206, 20220620-8, scientific research and technology key R&D plan of Nanning Liangqing district under grant number 202009, 202213, 202216, Guangxi young and middle-aged teachers’ scientific research basic ability improvement project under grant number 2019KY0320.

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Authors and Affiliations

  1. School of Basic Medicine, Guangxi University of Traditional Chinese Medicine, Nanning, 530001, China

    Lin Bai, Yaping Zhang, Changmin Zheng, Shifu Xu, Yining He, Guangqiang Yu, Delun Huang, Yulin Huang & Mingxing Li

  2. Guangxi Key Laboratory of Marine Drugs, Nanning, 530200, China

    Lin Bai

  3. Nanning Second People’s Hospital, Reproductive Medicine Center, Nanning, 530002, China

    Changlong Xu

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  1. Lin Bai
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  2. Yaping Zhang
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  3. Changmin Zheng
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  4. Shifu Xu
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  5. Yining He
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  6. Guangqiang Yu
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  7. Delun Huang
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  8. Yulin Huang
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  9. Mingxing Li
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  10. Changlong Xu
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Correspondence to Changlong Xu.

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Bai, L., Zhang, Y., Zheng, C. et al. Tanshinone IIA protects mouse testes from heat stress injury by inhibiting apoptosis and TGFβ1/Smad2/Smad3 signaling pathway. Cell Stress and Chaperones 28, 749–759 (2023). https://doi.org/10.1007/s12192-023-01367-4

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