Nicotine induced autophagy of Leydig cells rather than apoptosis is the major reason of the decrease of serum testosterone. (July 2018)

• Record Type: Journal Article
• Authors: Zhao, Xianglong; Xu, Wangjie; Wu, Jiajie; Zhang, Dong; Abou-Shakra, Abdelrahman; Di, Ling; Wang, Zhaoxia; Wang, Lianyun; Yang, Fan; Qiao, Zhongdong
• Is Part Of: International journal of biochemistry & cell biology. Volume 100(2018)
• Page Start: 30
• Page End: 41
• Publication Date: 2018-07
• Subjects: Nicotine -- Testosterone -- Autophagy -- TCL1 -- Leydig cells; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2018.05.001
• Languages: English
• ISSNs: 1357-2725

Abstract

Highlights: Nicotine decreases mice serum testosterone by triggering testicular autophagy instead of apoptosis via TCL1-mTOR -autophagy pathway in Leydig cells. This study is among the first to use bioinformatics in the reproductive research area to draw the relationship between nicotine and testicular autophagy. This work as determined the relationship between nicotine and changes of testosterone concentrations in mouse sera on a molecular level. It was also found that the TCL1 promoter is methylated consequent to a cascade pathway induced by the presence of nicotine. Abstract: A new report has shown that nicotine exposure can decrease serum testosterone by apoptosis in Leydig cells; however, in our previous studies, we have almost never observed apoptosis there. The purpose of this study is to ensure whether apoptosis or autophagy in Leydig cells occurred. Our results confirmed again that the concentration of testosterone in the sera of nicotine-treated mice statistically decreased (P < 0.05). Furthermore, the data of single cell transcriptome indicated that the expression of autophagy-related genes was increased after nicotine exposure. Likewise, chemical and immune-histological staining demonstrated that autophagy of the Leydig cells increased after nicotine treatment rather than apoptosis. Apoptosis mainly exists in spermatids. Further, the expression of autophagy-related genes, such as Beclin1 and LC3, were up-regulated after nicotine exposure (P < 0.05). Additionally, the data of transmission electron microscopy showed more autophagosomes in the Leydig cells of the nicotine-exposed groups than the cells of the control groups. Moreover, immunofluorescent staining of LC3 in the TM3 Leydig cell line indicated that rapamycin and nicotine exposure up-regulates the autophagy phenotype/process and down-regulates their testosterone synthesis. In addition, the methylation level of the promoter region of TCL1 is increased in the nicotine-treated group compared to the control group, consequently decreasing the expression of TCL1 . In conclusion, the autophagy in Leydig cells induced by nicotine, which is set by the hyper-methylation of the TCL1 promoter region via the TCL1 - mTOR -autophagy signaling pathway.