title: Glycidamide inhibits progesterone production through reactive oxygen species-induced apoptosis in R2C Rat Leydig Cells.
abstract: The food contaminant acrylamide (AA) is usually recognized as a probable human carcinogen. In addition, AA has also been found able to induce male infertility in animals. Interestingly, resent research work revealed that the toxic effect of AA on the ability of male reproduction in vivo may due to glycidamide (GA) which is the metabolite of AA. In this study, R2C Leydig cells was used to investigate the toxic effects of GA on progesterone production. GA caused dose-dependent inhibition on the cell growth, with IC25, IC50,and IC75values found at 0.635, 0.872, and 1.198 mM, respectively. The results of single cell gel/Comet assay showed that GA significantly induced early-phase cell apoptosis, reduced progesterone production, as well as decreasing the protein expression of steroidogenic acute regulatory (StAR) in R2C cells. Furthermore, GA induced overproduction of intracellular reactive oxygen species (ROS), upregulated Bax expression, decreased mitochondrial membrane potential, and triggered mitochondria-mediated cell apoptosis. Consequently, the downstream effector caspase-3 was activated, resulting in Leydig cells apoptosis. Overall, our results showed that GA could damage R2C Leydig cells by the lesion of the ability of progesterone genesis and inducing cells apoptosis.
authors.affiliation: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou, 510632, China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Li
authors.affiliation: Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.
authors.forename: Jianxia
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou, 510632, China.
authors.forename: Feiyan
authors.initials: F
authors.lastname: Zou
authors.affiliation: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou, 510632, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Bai
authors.affiliation: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou, 510632, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou, 510632, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Jiao
authors.affiliation: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou, 510632, China.
authors.forename: Shiyi
authors.initials: S
authors.lastname: Ou
authors.affiliation: China Rural Technology Development Center, Beijing, 100045, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou, 510632, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou, 510632, China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: 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.forename: Weibin
authors.initials: W
authors.lastname: Bai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004852:Epoxy Compounds / Q000494:pharmacology*; D007985:Leydig Cells / Q000187:drug effects*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011374:Progesterone / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000633:toxicity*
chemical_list: D004852:Epoxy Compounds; D017382:Reactive Oxygen Species; D011374:Progesterone; C071834:glycidamide
keywords: Apoptosis; Glycidamide; Mitochondrial membrane potential; Progesterone; R2C cells; ROS