title: G9a-mediated histone methylation regulates cadmium-induced male fertility damage in pubertal mice.
abstract: 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.
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Chunhai
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Mindi
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health and Health Management, Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Pi
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China. Electronic address: yuzping_tmmu@126.com.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China. Electronic address: lunazhou00@163.com.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001381:Azepines / Q000494:pharmacology; D015153:Blotting, Western; D019256:Cadmium Chloride / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D007248:Infertility, Male / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008098:Litter Size; D008297:Male; D008745:Methylation; D008810:Mice, Inbred C57BL; D011799:Quinazolines / Q000494:pharmacology; D046468:Sexual Development; D013076:Sperm Count; D013737:Testis / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D001381:Azepines; C518299:BIX 01294; D004791:Enzyme Inhibitors; D006657:Histones; D011799:Quinazolines; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D019256:Cadmium Chloride
keywords: Cadmium; G9a; Histone methylation; Male fertility; Testicular cell apoptosis