Effects of 4-nonylphenol on spermatogenesis and induction of testicular apoptosis through oxidative stress-related pathways.
This study tested the hypothesis that prepubertal exposure to 4-nonylphenol (NP) affects reproductive function in male rats. Twenty-four rats at five-weeks-old were randomly divided into four groups and treated with NP at varying concentrations (0, 5, 20, and 60mg/kg/2d) for thirty days by intra-peritoneal injection. 60mg/kg NP induced spermatogenic degeneration and pronounced deficits in epididymal sperm count, motility and function, whereas potentially stimulatory effects were observed at 5 NPmg/kg. Moreover, 60mg/kg NP resulted in a significant reduction in fructose, FSH and LH; induced apoptosis related to oxidative stress; inhibited mRNA and protein levels of Bcl-2 and PCNA; as well as the additional up-regulation of p53, Bax, Apaf-1, cytochrome c, cleaved-caspase-3, Fas and FasL expression. Our data suggest potentially hormetic effects of NP on spermatogenic function. High-dose NP impairs testicular development and function by reducing cell proliferation and inducing apoptosis involving oxidative stress-related p53-Bcl-2/Bax and -Fas/FasL pathways.
MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Peng
P
Duan
Department of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China.
Chunhui
C
Hu
Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Bailrigg, Lancaster LA1 4YQ, UK.
Holly J
HJ
Butler
MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Chao
C
Quan
MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Wei
W
Chen
MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Wenting
W
Huang
MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Sha
S
Tang
MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Wei
W
Zhou
MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Meng
M
Yuan
Department of epidemiology and health statistics, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan 430030, China.
Yuqin
Y
Shi
Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Bailrigg, Lancaster LA1 4YQ, UK.
Francis L
FL
Martin
MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: yangkd@mails.tjmu.edu.cn.
Kedi
K
Yang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D053222:Fas Ligand Protein / Q000235:genetics; D005640:Follicle Stimulating Hormone / Q000097:blood; D005632:Fructose / Q000378:metabolism; D059165:Hormesis / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D017207:Rats, Sprague-Dawley; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D019014:fas Receptor / Q000235:genetics
D053222:Fas Ligand Protein; C491898:Fas protein, rat; C505662:Faslg protein, rat; D010636:Phenols; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D005632:Fructose; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D020169:Caspases; C041594:4-nonylphenol
4-Nonylphenol; Apoptosis; Hormetic effect; Intrinsic and extrinsic apoptotic pathways; Oxidative stress; Rats; Reproductive toxicity