Paternal ethanol exposure and behavioral abnormities in offspring: associated alterations in imprinted gene methylation.
Research confirms that maternal ethanol (EtOH) exposure can induce physical and mental disorders in offspring, yet the effect of paternal ethanol exposure on offspring is unclear. Methylation alterations in imprinted genes may be related to the well-documented teratogenic effects of ethanol. Here, we report that ethanol (0, 1.1, 3.3 g/kg) was administered intragastrically to male mice and a behavioral study was performed on their F1 generation. Data show that F1 mice with fathers exposed to the highest dose of ethanol had delayed cognitive performance and increased anxiety and depression. A specific circling behavior was observed in the offspring of the paternally ethanol-exposed group. The degree of methylation and mRNA expression of H19, Peg3, Ndn and Snrpn were assessed in paternal sperm and in the cerebral cortices of each offspring. It did affect methylation in paternal sperm (H19 and Peg3) and in the offspring's cerebral cortices (CpG7 and CpG11 in Peg3 and Snrpn), but the level of mRNA expression has not changed. In the circling mice, the highest ethanol exposure increase in methylation (CpG 1, 2, 7 and 11) and decreases in mRNA of Peg3.Thus, chronic paternal ethanol exposure can affect the methylation of imprinted genes in sire sperm that may be passed on to offspring, giving rise to mental deficits.
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, China. Electronic address: feifeiliang2007@163.com.
Fei
F
Liang
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, China.
Lei
L
Diao
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, China.
Jun
J
Liu
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, China.
Nan
N
Jiang
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, China.
Jin
J
Zhang
Children Hospital, Fudan University, 200032, China.
Huijun
H
Wang
Children Hospital, Fudan University, 200032, China.
Wenhao
W
Zhou
Children Hospital, Fudan University, 200032, China.
Guoying
G
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, China; Children Hospital, Fudan University, 200032, China. Electronic address: duanma@fudan.edu.cn.
Duan
D
Ma
D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002540:Cerebral Cortex; D018899:CpG Islands / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D002658:Developmental Disabilities / Q000139:chemically induced*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D001523:Mental Disorders / Q000139:chemically induced*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018812:Paternal Exposure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology
D002492:Central Nervous System Depressants; 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; C069766:necdin; D000431:Ethanol
Cognition; Imprinted genes; Methylation; Mood; Offspring; Paternal ethanol exposure