Nonylphenol induced apoptosis and autophagy involving the Akt/mTOR pathway in prepubertal Sprague-Dawley male rats in vivo and in vitro.
This research explores the detrimental effect of nonylphenol (NP) to prepubertal Sprague-Dawley male rats in vivo and in vitro. Herein, forty-two 3-week-old rats were randomly divided into six groups, which were treated with NP (0, NAC, 25, 50, 100, 100+NACmg/kg/2d for 30 consecutive days) by intraperitoneal injection. NP induced a reduction in testosterone (15.58%, 17.23%, 13.38% in 25, 50, 100mg/kg group, respectively), triggered apoptosis related to oxidative stress, and disturbed mRNA and/or protein levels of PI3K, PTEN, PDK1, p-Akt, p-mTOR, p70S6K, caspase-3, LC3B. NP induced morphological abnormality in epididymal sperm (2.00-, 3.02-fold in 50, 100mg/kg group, respectively). Pretreatment with NAC, attenuated NP-induced ROS production; recovered testosterone in serum, and ameliorated toxic effect in epididymal sperm. Sertoli cells were isolated, purified, treated with NP (0, 10, 20, and 30μM) for 12h. NP disturbed mRNA and/or protein levels of caspase-3, cleave-caspase-3, LC3B involving the PI3K/Akt/mTOR pathway. It also decreased protein levels of ABP, FSHR, N-cadherin, transferrin, vimentin; disturbed the gene levels of all, but vimentin. Pretreatment with wortmannin, alleviated an NP-induced reduction in protein levels of PI3K and PTEN. In conclusion, excess NP exposure induces apoptosis and autophagy, causes reproductive lesions involving the PI3K/AKT/mTOR pathway both in vivo and in vitro. It also triggers oxidative stress and hormonal deficiency, reduces semen quality.
MOE Key Laboratory of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China.
Wenting
W
Huang
MOE Key Laboratory of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China.
Chao
C
Quan
MOE Key Laboratory of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China.
Peng
P
Duan
MOE Key Laboratory of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China.
Sha
S
Tang
MOE Key Laboratory of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China.
Wei
W
Chen
MOE Key Laboratory of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China. Electronic address: yang1981505@126.com.
Kedi
K
Yang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000187:drug effects / Q000648:ultrastructure; D015398:Signal Transduction / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013739:Testosterone / Q000097:blood; D062725:Tight Junction Proteins / Q000187:drug effects
D052244:Endocrine Disruptors; D012739:Gonadal Steroid Hormones; D010636:Phenols; D062725:Tight Junction Proteins; D013739:Testosterone; C025256:nonylphenol; C546845:mTOR protein, rat; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
Apoptosis; Autophagy; Endocrine disruptor; Nonylphenol; Reproductive toxicity; Secretory function