Paternal alcohol exposure affects sperm cytosine methyltransferase messenger RNA levels
Paternal alcohol exposure affects sperm cytosine methyltransferase messenger RNA levels
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DOI：
10.1111/j.1530-0277.2002.tb02544.x
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发表时间：
2002-03-01
影响因子：
3.2
通讯作者：
Abel, EL
中科院分区：
文献类型：
--
作者：
Bielawski, DM;Zaher, FM;Abel, EL
背景资料：虽然父亲的酒精暴露已被证明会影响后代的生长和行为，这些影响的机制仍然有待阐明。本研究探讨了一种可能的机制，即改变基因组印迹所反映的变化，精子胞嘧啶甲基转移酶信使RNA（mRNA）levels.Methods：雄性大鼠进行了治疗，用酒精9周前繁殖。计算胎儿数量并称重，检测父亲精子中胞嘧啶甲基转移酶mRNA水平的变化。酒精并不影响交配，繁殖力，或产仔数，但它确实导致显着降低平均胎儿体重，增加胎儿发育不良的发生率在后代，并降低胞嘧啶甲基转移酶mRNA水平在父亲的精子，与配对喂养和随意对照。酒精诱导的胞嘧啶甲基转移酶mRNA水平的降低可能反映了DNA甲基化降低引起的基因组印记改变，反过来，可能导致通常沉默的父系等位基因的表达，并且可能是父系酒精效应的机制。
Background: Although paternal alcohol exposure has been shown to affect the growth and behavior of offspring, the mechanisms underlying these effects still remain to be elucidated. This study examines one possible mechanism, namely, altered genomic imprinting as reflected by changes in sperm cytosine methyltransferase messenger RNA (mRNA) levels.Methods: Male rats were treated with alcohol for 9 weeks before breeding. Resulting fetuses were counted and weighed, and paternal sperm was examined for changes in cytosine methyltransferase mRNA levels.Results. Alcohol did not affect mating, fecundity, or litter size, but it did result in significantly decreased mean fetal weight, increased fetal runt incidence in offspring, and decreased cytosine methyltransferase mRNA levels in paternal sperm, compared with pair-fed and ad libitum controls.Conclusions: Alcohol-induced reductions in cytosine methyltransferase mRNA levels may reflect altered genomic imprinting caused by reduced DNA methylation, which, in turn, may lead to the expression of normally silent paternal alleles and may be a mechanism for paternal alcohol effects.