Chronic exposure to ethanol in male mice may be associated with hearing loss in offspring.
Although paternal ethanol (EtOH) abuse has been shown to affect the growth and behavior of offspring, the exact molecular and mechanistic basis remains largely unclear. Methylation alterations in imprinted genes may be related to well-documented teratogenic effects of ethanol. Here we show that chronic paternal ethanol exposure increases the susceptibility to abnormal behavior in offspring through male game epigenetic alteration. In our study, different doses of ethanol (0, 1.1, 3.3 g kg-1 ) were administered intra-gastrically to male mice and decreased sperm motility was found in the highest ethanol-exposed group compared with the controls. Data also showed a dose-dependent increase in deaf mice of the paternally ethanol-exposed groups. The methylation of H19, Peg3, Ndn and Snrpn was assessed in paternal spermatozoa and in the cerebral cortices of deaf mice. EtOH affected methylation of Peg3 (CpG 3, 7 and 9) in paternal spermatozoa and in the cerebral cortices of deaf mice, but the level of mRNA expression did not change, suggesting that other gene regulation may be involved in these processes. Overall, chronic paternal ethanol exposure could alter the methylation of imprinted genes in sire spermatozoa that could also be passed on to offspring, giving rise to developmental disorders. Our results provide possible epigenetic evidence for a paternal ethanol exposure contribution to Fetal Alcohol Syndrome (FAS).
Fei
F
Liang
Lei
L
Diao
Nan
N
Jiang
Jin
J
Zhang
Hui-Jun
HJ
Wang
Wen-Hao
WH
Zhou
Guo-Ying
GY
Huang
Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032; Cardiovascular Center, Children's Hospital of Fudan University, Shanghai 201102, China.
Duan
D
Ma
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D003638:Deafness / Q000235:genetics; D000431:Ethanol / Q000494:pharmacology*; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D018392:Genomic Imprinting / Q000187:drug effects*; D006309:Hearing / Q000187:drug effects* / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics; D018812:Paternal Exposure; D062085:RNA, Long Noncoding / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism; D055517:snRNP Core Proteins / Q000187:drug effects / Q000235:genetics
D000891:Anti-Infective Agents, Local; C094335:H19 long non-coding RNA; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C097901:Peg3 protein, mouse; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C069766:necdin; D055517:snRNP Core Proteins; D000431:Ethanol