Ginkgo biloba extract alleviates deltamethrin-induced testicular injury by upregulating SKP2 and inhibiting Beclin1-independent autophagy.

Autor: Wang H; Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, PR China., Yang F; Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, PR China., Ye J; Nanchang Institute of Technology Medical College, No. 901, Hero Avenue, Nanchang Economic Development Zone, Nanchang 330044, Jiangxi, PR China., Dai X; Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, PR China., Liao H; Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, PR China., Xing C; Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, PR China., Jiang Z; Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, PR China., Peng C; Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, PR China., Gao F; Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, PR China., Cao H; Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, PR China. Electronic address: chbin20020804@jxau.edu.cn.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Dec; Vol. 135, pp. 156245. Date of Electronic Publication: 2024 Nov 09.
DOI: 10.1016/j.phymed.2024.156245
Abstrakt: Background: Male infertility is a worldwide concern that is associated with a decline in sperm quality. Environmental pollutants such as deltamethrin (DM) have harmful effects on male reproductive organs. By maintaining intracellular redox homeostasis, ginkgo biloba extract (GBE) can alleviate male reproductive dysfunction. However, research on the mechanisms by which GBE alleviates reproductive toxicity induced by DM is limited.
Purpose: In this study, we investigated whether GBE can alleviate DM-induced testicular and Sertoli cell reproductive toxicity by modulating SKP2 and Beclin1, thus providing a theoretical basis for the development of novel therapeutic approaches.
Study Design: We explored the role of GBE in mitigating DM-induced testicular damage, with a specific focus on the intricate involvement of ubiquitination and autophagy.
Methods: An experimental model was constructed using ICR male mice and the TM4 cell line. Tissue, cellular, and sperm morphological changes were observed through methods such as Hematoxylin and Eosin (H&E) staining, Periodate-Schiff (PAS) staining, ultrastructural observation, immunohistochemistry, and immunofluorescence. Enzyme and hormone levels were measured, and gene and protein levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting techniques.
Results: In vivo experiments showed that DM exposure led to decreased sex hormone levels, increased seminiferous tubule diameter and impaired spermatogenesis. Meanwhile, DM exposure was found to decrease ubiquitination levels, leading to mitochondrial damage and further escalation of mitochondrial autophagy. Furthermore, in the DM-induced cell model, the upregulation of Beclin1 expression was associated with the inhibition of the ubiquitin‒proteasome system (UPS) and SKP2, thereby exacerbating autophagy. However, GBE has demonstrated notable efficacy in alleviating the reproductive toxicity induced by DM.
Conclusion: Our findings highlighted that SKP2 is a key regulator of Beclin1-independent autophagy and that GBE exerts therapeutic effects by upregulating SKP2 and inhibiting Beclin1 activation, which ameliorates autophagy and reduces DM-induced testicular damage.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier GmbH.)
Databáze: MEDLINE
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