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Nano-selenium Alleviates Cadmium-Induced Mouse Leydig Cell Injury, via the Inhibition of Reactive Oxygen Species and the Restoration of Autophagic Flux

  • Reproductive Biology: Original Article
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Abstract

Cadmium (Cd) is a well-known environmental pollutant that can contribute to male reproductive toxicity through oxidative stress. Nano-selenium (Nano-se) is an active single body of selenium with strong antioxidant properties and low toxicity. Some studies have addressed the potential ameliorative effect of Nano-se against Cd-induced testicular toxicity; however, the underlying mechanisms remain to be investigated. This study aimed to explore the protective effect of Nano-se on Cd-induced mouse testicular TM3 cell toxicity by regulating autophagy process. We showed that cadmium exposure to TM3 cells inhibited cell viability and elevated the level of reactive oxygen species (ROS) generation. Morphology observation by transmission electron microscope and the presence of mRFP-GFP-LC3 fluorescence puncta demonstrated that cadmium increased autophagosome formation and accumulation in TM3 cells, resulting in blocking the autophagic flux of TM3 cells. Meanwhile, cadmium remarkably increased the ratio of LC3-II to LC3-I protein expression (2.07 ± 0.31) and the Beclin-1 protein expression (1.97 ± 0.40) in TM3 cells (P < 0.01). Pretreatment with Nano-se significantly reduced Cd-induced TM3 cell toxicity (P < 0.01). Furthermore, Nano-se treatment reversed Cd-induced ROS production and autophagosome accumulation, and autophagy as evidenced by the ratio of LC3-II to LC3-I and Beclin-1 expression. In addition, ROS scavenger, N-acetyl-L-cysteine (NAC) or autophagy inhibitor, 3-methyladenine (3-MA) reversed cadmium-induced ROS generation, autophagosome accumulation, and autophagy-related protein expression levels, which confirmed that cadmium induced TM3 cell injury via ROS signal pathway and blockage of autophagic flux. Collectively, our results reveal that Nano-se attenuates Cd-induced TM3 cell toxicity through the inhibition of ROS production and the amelioration of autophagy disruption.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (NO. 81302429), Postgraduate and Undergraduate Research & Practice Innovation Program of Jiangsu Province (KYCX19_2128, KYCX20_2500, KYCX21_2726, and 202010313060Y), and Jiangsu Overseas Visiting Scholar Program for University Prominent Young & Middle-aged Teachers and Presidents.

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  1. **ndi Hu and Rui Lin contributed equally to this work.

Authors and Affiliations

  1. Department of Nutrition, School of Public Health, Xuzhou Medical University, No. 209 Tongshan Road, Yunlong Area, Xuzhou, 221004, Jiangsu Province, China

    **ndi Hu, Rui Lin, Chaoqin Zhang, Ya**g Pian, Haolong Luo, Li Zhou, Jihong Shao & **angmei Ren

  2. Key Lab of Environment and Health, School of Public Health, Xuzhou Medical University, Xuzhou, China

    **ndi Hu, Rui Lin, Chaoqin Zhang, Ya**g Pian, Haolong Luo, Li Zhou, Jihong Shao & **angmei Ren

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Correspondence to **angmei Ren.

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Hu, X., Lin, R., Zhang, C. et al. Nano-selenium Alleviates Cadmium-Induced Mouse Leydig Cell Injury, via the Inhibition of Reactive Oxygen Species and the Restoration of Autophagic Flux. Reprod. Sci. 30, 1808–1822 (2023). https://doi.org/10.1007/s43032-022-01146-z

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