PMID- 27060504
OWN - NLM
STAT- MEDLINE
DCOM- 20170131
LR  - 20170131
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 252
DP  - 2016 Jun 11
TI  - G9a-mediated histone methylation regulates cadmium-induced male fertility damage 
      in pubertal mice.
PG  - 11-21
LID - S0378-4274(16)30055-8 [pii]
LID - 10.1016/j.toxlet.2016.04.004 [doi]
AB  - Increasing evidence suggests that cadmium (Cd) is associated with male fertility 
      damage. However, the effects of histone modification on Cd-induced male fertility 
      damage remain obscure. This study aims to evaluate the roles of histone 
      methylation mediated by euchromatin histone methyltransferase (EHMT2/G9a) in 
      regulating Cd-induced male fertility damage. We exposed 4-week-old male C57BL/6J 
      mice to Cd by intraperitoneal injection at 2mg/kg for 1, 3 and 5days. Our data 
      showed that Cd exposure decreased the numbers of impregnated females and litter 
      sizes, which was concomitant with sperm count reduction, histological changes in 
      the cauda epididymal ducts and seminiferous epithelium, and testicular cell 
      apoptosis as evaluated by terminal dUTP nick-end labeling (TUNEL) assay and 
      immunoblotting with increased levels of cleaved caspase 3, PARP and Bax and a 
      decreased level of Bcl-2. Cd-induced male fertility damage was accompanied by 
      enhanced G9a activity followed by increased histone H3 lysine 9 monomethylation 
      (H3K9me1) and dimethylation (H3K9me2) in testes. Furthermore, inhibition of G9a 
      by BIX-01294 normalized H3K9me1 and H3K9me2 to basal levels and prevented 
      Cd-induced male fertility damage and testicular cell apoptosis. Our present study 
      revealed that G9a-mediated histone methylation plays a critical role in 
      Cd-induced male fertility damage and testicular cell apoptosis.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - Li, Min
AU  - Li M
AD  - Department of Occupational Health, Third Military Medical University, Chongqing 
      400038, People's Republic of China.
FAU - Liu, Chuan
AU  - Liu C
AD  - Department of Occupational Health, Third Military Medical University, Chongqing 
      400038, People's Republic of China.
FAU - Yang, Lingling
AU  - Yang L
AD  - Department of Occupational Health, Third Military Medical University, Chongqing 
      400038, People's Republic of China.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Department of Occupational Health, Third Military Medical University, Chongqing 
      400038, People's Republic of China.
FAU - Chen, Chunhai
AU  - Chen C
AD  - Department of Occupational Health, Third Military Medical University, Chongqing 
      400038, People's Republic of China.
FAU - He, Mindi
AU  - He M
AD  - Department of Occupational Health, Third Military Medical University, Chongqing 
      400038, People's Republic of China.
FAU - Lu, Yonghui
AU  - Lu Y
AD  - Department of Occupational Health, Third Military Medical University, Chongqing 
      400038, People's Republic of China.
FAU - Feng, Wei
AU  - Feng W
AD  - Department of Occupational and Environmental Health, School of Public Health and 
      Health Management, Chongqing Medical University, Chongqing 400016, People's 
      Republic of China.
FAU - Pi, Huifeng
AU  - Pi H
AD  - Department of Occupational Health, Third Military Medical University, Chongqing 
      400038, People's Republic of China.
FAU - Zhang, Yanwen
AU  - Zhang Y
AD  - Department of Occupational Health, Third Military Medical University, Chongqing 
      400038, People's Republic of China.
FAU - Zhong, Min
AU  - Zhong M
AD  - Department of Occupational Health, Third Military Medical University, Chongqing 
      400038, People's Republic of China.
FAU - Yu, Zhengping
AU  - Yu Z
AD  - Department of Occupational Health, Third Military Medical University, Chongqing 
      400038, People's Republic of China. Electronic address: yuzping_tmmu@126.com.
FAU - Zhou, Zhou
AU  - Zhou Z
AD  - Department of Occupational Health, Third Military Medical University, Chongqing 
      400038, People's Republic of China. Electronic address: lunazhou00@163.com.
LA  - eng
PT  - Journal Article
DEP - 20160406
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Azepines)
RN  - 0 (BIX 01294)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histones)
RN  - 0 (Quinazolines)
RN  - EC 2.1.1.43 (G9a protein, mouse)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - J6K4F9V3BA (Cadmium Chloride)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Azepines/pharmacology
MH  - Blotting, Western
MH  - Cadmium Chloride/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Fertility/*drug effects
MH  - Fluorescent Antibody Technique
MH  - Histone-Lysine N-Methyltransferase/antagonists & inhibitors/*metabolism
MH  - Histones/*metabolism
MH  - In Situ Nick-End Labeling
MH  - Infertility, Male/*chemically induced/enzymology/pathology/physiopathology
MH  - Litter Size
MH  - Male
MH  - Methylation
MH  - Mice, Inbred C57BL
MH  - Quinazolines/pharmacology
MH  - Sexual Development
MH  - Sperm Count
MH  - Testis/*drug effects/enzymology/pathology/physiopathology
MH  - Time Factors
OTO - NOTNLM
OT  - Cadmium
OT  - G9a
OT  - Histone methylation
OT  - Male fertility
OT  - Testicular cell apoptosis
EDAT- 2016/04/10 06:00
MHDA- 2017/02/01 06:00
CRDT- 2016/04/10 06:00
PHST- 2016/01/15 00:00 [received]
PHST- 2016/03/18 00:00 [revised]
PHST- 2016/04/05 00:00 [accepted]
PHST- 2016/04/10 06:00 [entrez]
PHST- 2016/04/10 06:00 [pubmed]
PHST- 2017/02/01 06:00 [medline]
AID - S0378-4274(16)30055-8 [pii]
AID - 10.1016/j.toxlet.2016.04.004 [doi]
PST - ppublish
SO  - Toxicol Lett. 2016 Jun 11;252:11-21. doi: 10.1016/j.toxlet.2016.04.004. Epub 2016 
      Apr 6.