title: 1,3-Dichloro-2-propanol inhibits progesterone production through the expression of steroidogenic enzymes and cAMP concentration in Leydig cells.
abstract: 1,3-Dichloro-2-propanol (1,3-DCP) is a well-known food processing contaminant that has been shown to impede male reproductive function. However, its mechanism of action remains elusive. In this study, the effects of 1,3-DCP on progesterone production were investigated using the R2C Leydig cell model. 1,3-DCP significantly reduced cell viability from 7.48% to 97.4% at doses comprised between 0.5 and 6mM. Single cell gel/comet assays and atomic force microscopy assays showed that 1,3-DCP induced early phase cell apoptosis. In addition, 1,3-DCP significantly reduced progesterone production detected by radioimmunoassay (RIA). The results from quantitative polymerase chain reaction and western blotting demonstrated that the mRNA expression levels of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase were significantly down-regulated in R2C cells. Particularly, the change rhythm of Star expression was highly consistent with progesterone production. Furthermore, the cyclic adenosine monophosphate (cAMP) and the mitochondrial membrane potential mediated by ROS, which are involved in regulating progesterone synthesis were also decreased in response to the 1,3-DCP treatment. Overall, the data presented here suggested that 1,3-DCP interferes with the male steroidogenic capacity mainly by down-regulating the level of cAMP and the key enzymes involved in the androgen synthesis pathway.
authors: Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China; Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou 510632, China.
authors: Jianxia
authors: J
authors: Sun
authors: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou 510632, China.
authors: Shun
authors: S
authors: Bai
authors: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou 510632, China. Electronic address: baiweibin@163.com.
authors: Weibin
authors: W
authors: Bai
authors: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou 510632, China.
authors: Feiyan
authors: F
authors: Zou
authors: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou 510632, China.
authors: Lei
authors: L
authors: Zhang
authors: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou 510632, China.
authors: Guoqiang
authors: G
authors: Li
authors: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou 510632, China.
authors: Yunfeng
authors: Y
authors: Hu
authors: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou 510632, China.
authors: Mingwei
authors: M
authors: Li
authors: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou 510632, China.
authors: Rian
authors: R
authors: Yan
authors: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou 510632, China. Electronic address: su_zhijian@126.com.
authors: Zhijian
authors: Z
authors: Su
authors: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou 510632, China.
authors: Yadong
authors: Y
authors: Huang
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010750:Phosphoproteins; D011374:Progesterone / Q000096:biosynthesis*; D051381:Rats; D000517:alpha-Chlorohydrin / Q000031:analogs & derivatives* / Q000633:toxicity; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; C033489:1,3-dichloro-2-propanol; D011374:Progesterone; D003577:Cytochrome P-450 Enzyme System; D000517:alpha-Chlorohydrin; D000242:Cyclic AMP; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase
keywords: 1,3-DCP; Mitochondrial membrane potential; Progesterone; ROS; cAMP