PMID- 37121744
OWN - NLM
STAT- MEDLINE
DCOM- 20230502
LR  - 20230502
IS  - 1880-3989 (Electronic)
IS  - 0388-1350 (Linking)
VI  - 48
IP  - 5
DP  - 2023
TI  - The mechanism of monobutyl phthalate -induced ferroptosis via TNF/IL6/STAT3 
      signal pathway in TM-3 cells.
PG  - 299-310
LID - 10.2131/jts.48.299 [doi]
AB  - As a common environmental endocrine disruptor, monobutyl phthalate (MBP) has been 
      connected to reports of ROS accumulation, sperm destruction and reproductive 
      damage. However, the specific mechanism of reproductive injury caused by MBP 
      remains uncertain. Ferroptosis is a non-apoptotic, controlled oxidative 
      damage-related cell death that is usually connected with reactive oxygen species 
      and lipid peroxidation. In this work, to evaluate the mechanism of MBP-induced 
      ferroptosis in reproductive damage, bioinformation analysis and experimental 
      validation were used. Based on bioinformatics analysis, the interleukin-6 (IL-6) 
      and signal transducer and activator of transcription 3 (STAT3) genes may be 
      involved in the tumor necrosis factor (TNF) signaling pathway, which controls 
      inflammation. Experimental study validated the significance of IL6 and STAT3 in 
      MBP-induced ferroptosis. Western blotting and quantitative real-time PCR revealed 
      that Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4), Tumor necrosis 
      factor-alpha (TNF-alpha), IL6, and STAT3 were all elevated with treatment of MBP, but 
      Glutathione peroxidase 4 was significantly decreased. To determine the 
      participation of IL6/STAT3, we added the ferroptosis inhibitor Ferrastain-1 
      (Fer-1) and the IL6/STAT3 pathway inhibitor Angoline. In conclusion, we found 
      that MBP induced ferroptosis in TM3 cells to damage male reproductive system 
      through the TNF/IL6/STAT signal pathway, resulting in lipid peroxidation and iron 
      metabolite degradation.
FAU - Guo, Xiaoying
AU  - Guo X
AD  - Department of Occupational and Environmental Health, School of Public Health and 
      Management, Ningxia Medical University, China.
AD  - Key Laboratory of Environmental Factors and Chronic Disease Control, School of 
      Public Health and Management, Ningxia Medical University, China.
AD  - Anyue County Center for Disease Control and Prevention, China.
FAU - Hao, Yu
AU  - Hao Y
AD  - Department of Occupational and Environmental Health, School of Public Health and 
      Management, Ningxia Medical University, China.
AD  - Key Laboratory of Environmental Factors and Chronic Disease Control, School of 
      Public Health and Management, Ningxia Medical University, China.
FAU - Ma, Huiying
AU  - Ma H
AD  - Department of Occupational and Environmental Health, School of Public Health and 
      Management, Ningxia Medical University, China.
AD  - Key Laboratory of Environmental Factors and Chronic Disease Control, School of 
      Public Health and Management, Ningxia Medical University, China.
FAU - Li, Hai
AU  - Li H
AD  - Department of Colorectal Surgery, General Hospital of Ningxia Medical University, 
      China.
AD  - College of Clinical Medicine, Ningxia Medical University, China.
FAU - Li, Liping
AU  - Li L
AD  - Department of Occupational and Environmental Health, School of Public Health and 
      Management, Ningxia Medical University, China.
AD  - Key Laboratory of Environmental Factors and Chronic Disease Control, School of 
      Public Health and Management, Ningxia Medical University, China.
FAU - Yan, Fengmei
AU  - Yan F
AD  - Department of Occupational and Environmental Health, School of Public Health and 
      Management, Ningxia Medical University, China.
AD  - Key Laboratory of Environmental Factors and Chronic Disease Control, School of 
      Public Health and Management, Ningxia Medical University, China.
FAU - Huang, Jing
AU  - Huang J
AD  - Department of Occupational and Environmental Health, School of Public Health and 
      Management, Ningxia Medical University, China.
AD  - Key Laboratory of Environmental Factors and Chronic Disease Control, School of 
      Public Health and Management, Ningxia Medical University, China.
FAU - Li, Ling
AU  - Li L
AD  - Department of Occupational and Environmental Health, School of Public Health and 
      Management, Ningxia Medical University, China.
AD  - Key Laboratory of Environmental Factors and Chronic Disease Control, School of 
      Public Health and Management, Ningxia Medical University, China.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - J Toxicol Sci
JT  - The Journal of toxicological sciences
JID - 7805798
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - ZI46LWZ45G (monobutyl phthalate)
RN  - 0 (STAT3 Transcription Factor)
SB  - IM
MH  - Male
MH  - Humans
MH  - *Ferroptosis/physiology
MH  - Interleukin-6/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
MH  - STAT3 Transcription Factor/genetics/metabolism
MH  - Semen/metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - Ferroptosis
OT  - Inflammation
OT  - Male reproduction
OT  - Monobutyl phthalate
EDAT- 2023/05/01 00:42
MHDA- 2023/05/02 06:42
CRDT- 2023/04/30 21:24
PHST- 2023/05/02 06:42 [medline]
PHST- 2023/05/01 00:42 [pubmed]
PHST- 2023/04/30 21:24 [entrez]
AID - 10.2131/jts.48.299 [doi]
PST - ppublish
SO  - J Toxicol Sci. 2023;48(5):299-310. doi: 10.2131/jts.48.299.