Bielawski Dawn M, Zaher Fadi M, Svinarich David M, Abel Ernest L
Hutzel Hospital, Department of Pediatrics, Wayne State University, Detroit, MI 48201, USA.
Alcohol Clin Exp Res. 2002 Mar;26(3):347-51.
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.
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.
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.
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.
尽管已有研究表明父亲饮酒会影响子代的生长和行为,但其潜在机制仍有待阐明。本研究探讨了一种可能的机制,即精子胞嘧啶甲基转移酶信使核糖核酸(mRNA)水平的变化所反映的基因组印记改变。
雄性大鼠在交配前接受为期9周的酒精处理。统计并称重所产胎儿,并检测父本精子中胞嘧啶甲基转移酶mRNA水平的变化。
与配对喂养和自由摄食对照组相比,酒精并未影响交配、生育力或窝仔数,但确实导致平均胎儿体重显著降低、子代中胎儿发育迟缓发生率增加,以及父本精子中胞嘧啶甲基转移酶mRNA水平降低。
酒精引起的胞嘧啶甲基转移酶mRNA水平降低可能反映了DNA甲基化减少导致的基因组印记改变,进而可能导致正常沉默的父本等位基因表达,这可能是父亲饮酒产生影响的一种机制。