title: Di-(2-ethylhexyl) phthalate induces apoptosis of GC-2spd cells via TR4/Bcl-2 pathway.
abstract: Di-(2-ethylhexyl) phthalate (DEHP) is a widely used environmental endocrine disruptor. Many studies have reported that DEHP exposure causes reproductive toxicity and cells apoptosis. However, the mechanism by which DEHP exposure causes male reproductive toxicity remains unknown. This study investigated the role of the testicular orphan nuclear receptor4 (TR4)/Bcl-2 pathway in apoptosis induced by DEHP, which resulted in reproductive damage. To elucidate the mechanism underpinning the male reproductive toxicity of DEHP, we sought to investigate apoptotic effects, expression levels of TR4/Bcl-2 pathway in GC-2spd cells, including TR4, Bcl-2 and caspase-3. GC-2spd cells were exposed to various concentrations of DEHP (0, 50, 100, or 200μM). The results indicated that, with the increase of the concentrations of DEHP, the survival rate of cell decreased gradually. DEHP exposure at over 100μM significantly induced apoptotic cell death. DEHP decreased SOD and GSH-Px activity in 200μM group. Compared to the control group, the mRNA levels of caspase-3 increased significantly, however, Bcl-2 mRNA decreased (P<0.05). In addition, there was a significant reduction in TR4, Bcl-2 and procaspase-3 protein levels. Taken together, these results lead us to speculate that in vitro exposure to DEHP might induce apoptosis in GC-2spd cells through the TR4/Bcl-2 pathway.
authors.affiliation: School of Public Health, Medical College, Wuhan University of Science and Technology, 947Heping Avenue, Wuhan 430081, PR China.
authors.forename: Lishan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pulmonary Medicine, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, PR China.
authors.forename: Jinchang
authors.initials: J
authors.lastname: Lu
authors.affiliation: School of Public Health, Medical College, Wuhan University of Science and Technology, 947Heping Avenue, Wuhan 430081, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Tang
authors.affiliation: School of Public Health, Medical College, Wuhan University of Science and Technology, 947Heping Avenue, Wuhan 430081, PR China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Fu
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13Hangkong Road, Wuhan 430030, Hubei, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Duan
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13Hangkong Road, Wuhan 430030, Hubei, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Quan
authors.affiliation: School of Public Health, Medical College, Wuhan University of Science and Technology, 947Heping Avenue, Wuhan 430081, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Public Health, Medical College, Wuhan University of Science and Technology, 947Heping Avenue, Wuhan 430081, PR China; Department of Obstetrics & Gynecology, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Public Health, Medical College, Wuhan University of Science and Technology, 947Heping Avenue, Wuhan 430081, PR China. Electronic address: changwei_428@sina.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Chang
authors.affiliation: School of Public Health, Medical College, Wuhan University of Science and Technology, 947Heping Avenue, Wuhan 430081, PR China. Electronic address: shiyuqin@wust.edu.cn.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2 / Q000378:metabolism*; D010968:Plasticizers / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2; D010968:Plasticizers; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D008315:Malondialdehyde; D004051:Diethylhexyl Phthalate; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D053148:Caspase 3
keywords: Bcl-2; Cells apoptosis; Di-(2-ethylhexyl) phthalate; GC-2spd cells; Testicular orphan nuclear receptor 4