{"title":"Naringenin Attenuates Bisphenol A-Induced Leydig Cell Damage by Activating Autophagy","authors":"Yousef Asadi-Fard, Layasadat Khorsandi, Elham Younesi, Mohammad Javad Khodayar, Abbass Heidari-Moghadam","doi":"10.1155/and/5537141","DOIUrl":null,"url":null,"abstract":"<p>The toxic effects of bisphenol A (BPA) on the male reproductive system have been shown in previous research. The impact of naringenin (NG) on BPA-induced Leydig cell (TM3 cell line) toxicity and its mechanism was examined in the present study. The TM3 cells were treated with BPA or NG in various groups for 48 h. To analyze the autophagy role of NG and BPA in TM3 cells, the cells were pretreated with 3-methyladenine (3-Ma), an autophagy inhibitor. The viability rate of TM3 cells notably decreased when exposed to the BPA group. BPA induces oxidative stress in TM3 cells by diminishing crucial antioxidant components such as glutathione, superoxide dismutase, catalase, and glutathione peroxidase while simultaneously increasing the generation of reactive oxygen species (ROS). BPA significantly increased the Bax/Bcl-2 ratio and ROS generation while decreasing testosterone concentration. The expression of autophagy-inducer genes (ATG7, ATG5, and Beclin-1) and the ratio of LCSII/LC3I proteins were significantly reduced, while mTOR expression was increased in the BPA group. NG pretreatment decreased the Bax/Bcl-2 ratio and expression of mTOR, while increasing the LC3II/LC3I ratio and the expression of ATG5, ATG7, and Beclin-1 proteins. NG could also reverse testosterone and antioxidant levels of the BPA-intoxicated cells. Treatment with 3-Ma led to a significant decrease in cell viability in TM3 cells upon exposure to NG and BPA, whereas the untreated 3-Ma groups showed higher viability. In the presence of 3-Ma, NG caused a decline in testosterone levels and antioxidant biomarkers while raising the Bax/Bcl-2 ratio and ROS production in TM3 cells exposed to BPA. These results propose that NGs protect TM3 cells from BPA by enhancing autophagy and lowering apoptosis and oxidative stress.</p>","PeriodicalId":7817,"journal":{"name":"Andrologia","volume":"2025 1","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/and/5537141","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Andrologia","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/and/5537141","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ANDROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The toxic effects of bisphenol A (BPA) on the male reproductive system have been shown in previous research. The impact of naringenin (NG) on BPA-induced Leydig cell (TM3 cell line) toxicity and its mechanism was examined in the present study. The TM3 cells were treated with BPA or NG in various groups for 48 h. To analyze the autophagy role of NG and BPA in TM3 cells, the cells were pretreated with 3-methyladenine (3-Ma), an autophagy inhibitor. The viability rate of TM3 cells notably decreased when exposed to the BPA group. BPA induces oxidative stress in TM3 cells by diminishing crucial antioxidant components such as glutathione, superoxide dismutase, catalase, and glutathione peroxidase while simultaneously increasing the generation of reactive oxygen species (ROS). BPA significantly increased the Bax/Bcl-2 ratio and ROS generation while decreasing testosterone concentration. The expression of autophagy-inducer genes (ATG7, ATG5, and Beclin-1) and the ratio of LCSII/LC3I proteins were significantly reduced, while mTOR expression was increased in the BPA group. NG pretreatment decreased the Bax/Bcl-2 ratio and expression of mTOR, while increasing the LC3II/LC3I ratio and the expression of ATG5, ATG7, and Beclin-1 proteins. NG could also reverse testosterone and antioxidant levels of the BPA-intoxicated cells. Treatment with 3-Ma led to a significant decrease in cell viability in TM3 cells upon exposure to NG and BPA, whereas the untreated 3-Ma groups showed higher viability. In the presence of 3-Ma, NG caused a decline in testosterone levels and antioxidant biomarkers while raising the Bax/Bcl-2 ratio and ROS production in TM3 cells exposed to BPA. These results propose that NGs protect TM3 cells from BPA by enhancing autophagy and lowering apoptosis and oxidative stress.
期刊介绍:
Andrologia provides an international forum for original papers on the current clinical, morphological, biochemical, and experimental status of organic male infertility and sexual disorders in men. The articles inform on the whole process of advances in andrology (including the aging male), from fundamental research to therapeutic developments worldwide. First published in 1969 and the first international journal of andrology, it is a well established journal in this expanding area of reproductive medicine.