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出生时的表观遗传调控——剖宫产术后白细胞中DNA甲基化的改变

Epigenetic modulation at birth - altered DNA-methylation in white blood cells after Caesarean section.

作者信息

Schlinzig T, Johansson S, Gunnar A, Ekström T J, Norman M

机构信息

Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.

出版信息

Acta Paediatr. 2009 Jul;98(7):1096-9. doi: 10.1111/j.1651-2227.2009.01371.x.

Abstract

AIM

Delivery by C-section (CS) has been associated with increased risk for allergy, diabetes and leukaemia. Whereas the underlying cause is unknown, epigenetic change of the genome has been suggested as a candidate molecular mechanism for perinatal contributions to later disease risk. We hypothesized that mode of delivery affects epigenetic activity in newborn infants.

METHODS

A total of 37 newborn infants were included. Spontaneous vaginal delivery (VD) occurred in 21, and 16 infants were delivered by elective CS. Blood was sampled from the umbilical cord and 3-5 days after birth. DNA-methylation was analyzed in leucocytes.

RESULTS

Infants born by CS exhibited higher DNA-methylation in leucocytes compared with that of those born by VD (p < 0.001). After VD, newborn infants exhibited stable levels of DNA-methylation, as evidenced by comparing cord blood values with those 3-5 days after birth (p = 0.55). On postnatal days 3-5, DNA-methylation had decreased in the CS group (p = 0.01) and was no longer significantly different from that of VD (p = 0.10).

CONCLUSION

DNA-methylation is higher in infants delivered by CS than in infants vaginally born. Although currently unknown how gene expression is affected, or whether epigenetic differences related to mode of delivery are long-lasting, our findings open a new area of clinical research with potentially important public health implications.

摘要

目的

剖宫产与过敏、糖尿病和白血病风险增加有关。虽然潜在原因尚不清楚,但基因组的表观遗传变化已被认为是围产期对后期疾病风险产生影响的一种候选分子机制。我们假设分娩方式会影响新生儿的表观遗传活性。

方法

共纳入37名新生儿。其中21名自然阴道分娩,16名择期剖宫产。分别在脐带血采集时及出生后3 - 5天采集血液样本。对白细胞中的DNA甲基化进行分析。

结果

剖宫产出生的婴儿白细胞中的DNA甲基化水平高于阴道分娩出生的婴儿(p < 0.001)。阴道分娩后,新生儿的DNA甲基化水平保持稳定,通过比较脐带血与出生后3 - 5天的数值可证明这一点(p = 0.55)。在出生后3 - 5天,剖宫产组的DNA甲基化水平下降(p = 0.01),且与阴道分娩组不再有显著差异(p = 0.10)。

结论

剖宫产出生的婴儿DNA甲基化水平高于阴道分娩出生的婴儿。虽然目前尚不清楚基因表达如何受到影响,以及与分娩方式相关的表观遗传差异是否持久,但我们的研究结果开启了一个新的临床研究领域,可能具有重要的公共卫生意义。

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