Chlorocholine chloride induced testosterone secretion inhibition mediated by endoplasmic reticulum stress in primary rat Leydig cells. (1st March 2022)

• Record Type: Journal Article
• Authors: Xiao, Qianqian; Hou, Xiaohong; Kang, Chenping; Xu, Linglu; Yuan, Lilan; Zhao, Zhe; Meng, Qinghe; Jiang, Jianjun; Hao, Weidong
• Is Part Of: Toxicology letters. Volume 356(2022)
• Page Start: 161
• Page End: 171
• Publication Date: 2022-03-01
• Subjects: CCC Chlorocholine Chloride -- ER Endoplasmic reticulum -- GPR78 Glucose-regulated protein 78 -- CHOP C/EBP-homologous protein -- UBE2D1 ubiquitin-conjugating enzyme E2 D1 -- RNF 185 Ring finger protein 185 -- 4-PBA 4-phenyl butyric acid -- H2AFY H2A histone family, member Y -- H2AFY2 H2A histone family, member Y2 -- HIST1H1B a variant in linker histone family -- HIST2H2AB histone H2A, type 2B -- HIST2H4 Histone cluster 2, H4 -- H3F3C a member of H3 histone family -- MRL Maximum residue limits -- ADI Acceptable daily intake -- StAR Steroidogenic acute regulatory protein -- CYP11A1 Cytochrome P450 family 11 subfamily a member 1 -- HSD3B1 3β-hydroxysteroid dehydrogenase 1 -- CYP17A1 Cytochrome P450 17α-hydroxylase 1 -- HSD17B3 17β-hydroxysteroid dehydrogenase 3 -- GO Gene ontology -- KEGG Kyoto encyclopedia of genes and genomes -- PPI Protein and protein interaction -- HSD11B1 11β-hydroxysteroid dehydrogenase 1 -- cAMP Cyclic adenosine monophosphate; Chlorocholine chloride -- Testosterone -- Leydig cells -- Endoplasmic reticulum stress; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2021.12.018
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: CCC inhibited the testosterone secretion in primary rat Leydig cells in a dose-dependent manner. CCC triggered endoplasmic reticulum stress in Leydig cells in vitro . CCC-induced testosterone reduction depended on the activation of endoplasmic reticulum stress in primary Leydig cells. Abstract: Chlorocholine chloride (CCC) is well acknowledged as a plant growth regulator and may be considered as a potential environmental endocrine disrupting chemical. In our previous studies, it was found that CCC exposure at a pubertal stage reduced the serum and testicular levels of testosterone, decreased the sperm motility and delayed the puberty onset. However, the molecular mechanisms of CCC-induced testosterone secretion disorders remain unclear. In this study, we found that CCC exposure above 20 μg/mL inhibited the secretion of testosterone in Sprague-Dawley rats Leydig cells. Proteomic and pathway enrichment analysis indicated that CCC might induce endoplasmic reticulum (ER) stress. Western blot detection showed CCC exposure at 100, 200 μg/mL increased the protein level of glucose-regulated protein 78 (GPR78), C/EBP-homologous protein (CHOP), the ubiquitin-conjugating enzyme E2 D1 (UBE2D1) and the ring finger protein (RNF185) in the Leydig cells. The Leydig cells treated with 4-phenyl butyric acid (4-PBA), an ER stress inhibitor, rescued the testosterone secretion disorders and alleviated CCC-induced increase in the ER stress related protein levels at 200 μg/mL CCC treatment. Overall, CCC in vitro exposure might disturb testosterone production of Leydig cells and endoplasmic reticulum stress was involved in it.