妊娠期糖尿病患者胎盘PGC⁃1α和PDX1表达水平及甲基化状态与胎儿血糖水平的相关性
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江苏省妇幼保健科研课题(F201326)


Correlation between expression levels and methylation status in placental tissues of PGC⁃1α and PDX1 and fetal blood glucose in patients with gestational diabetes mellitus
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    摘要:

    目的:探讨妊娠期糖尿病(gestational diabetes mellitus,GDM)对胎盘中PGC-1α和PDX1表达水平及甲基化状态的影响,以及与胎儿血糖的相关性。方法:收集30例GDM孕妇的新生儿出生体重、胎盘重量等数据,同时收集30例无妊娠并发症和脐带异常的足月新生儿相应数据作为对照组。 在分娩后立即从胎盘滋养层组织收集样品,使用亚硫酸氢钠测序法定量检测PGC-1α和PDX1基因的DNA甲基化水平,逆转录定量PCR测量PGC-1α和PDX1 mRNA水平。 同时,测定胎盘组织的胰岛素、血糖和糖化血红蛋白(HbA1c)水平。结果:GDM组胎儿出生体重和胎盘重量均显著高于对照组(P <0.05)。 GDM组胎盘组织胰岛素、HbA1c和血糖水平显著高于对照组(P < 0.01)。 脐带血胰岛素水平与新生儿出生体重、胎盘重量、血糖和HbA1c呈正相关(r值分别为0.648、0.795、0.862、0.927,P 均<0.001)。与对照组比较,GDM组中PGC-1α和PDX1 mRNA的水平较低,PGC-1α基因甲基化水平较高(P < 0.05)。 胎盘组织中血糖水平与PGC-1α和PDX1 mRNA的表达呈负相关(r=-0.438,P=0.002;r=-0.373,P=0.007)。 结论:GDM孕妇PGC-1α基因表观遗传修饰的变化可能是其后代糖代谢异常的原因之一。

    Abstract:

    Objective:This study aims to investigate the effects of gestational diabetes mellitus(GDM)on the expression and methylation status of PGC-1α and PDX1 in placenta,and to explore the correlation between PGC-1α,PDX1 and fetal blood glucose. Methods:The birth weight and placental weight of 30 pregnant women with GDM were collected. The corresponding data of 30 full-term neonates without pregnancy complications and umbilical cord abnormalities were collected as control group. DNA and RNA were isolated from placental trophoblast tissue immediately after delivery. The DNA methylation levels of the PGC-1α and PDX1 genes were quantitatively detected using sodium bisulfite sequencing. PGC-1α and PDX1 mRNA levels were measured by reverse transcription quantitative PCR(qRT-PCR). At the same time,placental insulin,blood glucose and HbA1c levels were detected. Results:Fetal birth weight and placental weight were significantly higher in the GDM group than those in the control group(P < 0.05). Insulin,HbA1c and blood glucose levels were significantly higher in the GDM group than those in the control group(P < 0.01). Cord blood insulin levels were positively correlated with birth weight(r=0.648,P < 0.001),placental weight(r=0.795,P < 0.001),blood glucose(r=0.862,P < 0.001),and HbA1c(r=0.927,P < 0.001). The levels of PGC-1α and PDX1 mRNA were lower in the GDM group compared with the control group,and the PGC-1α gene methylation level was higher in the GDM group than that in the control group(P < 0.05). There was a negative correlation between blood glucose and mRNA expression of PGC-1α (r=-0.438,P=0.002) and PDX1(r=-0.373,P=0.007) in the placenta. Conclusion:The changes of epigenetic modification of PGC-1α gene in pregnant women with GDM may be one of the causes of abnormal glucose metabolism in their offspring.

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陈 超,施莉英,龚明霞.妊娠期糖尿病患者胎盘PGC⁃1α和PDX1表达水平及甲基化状态与胎儿血糖水平的相关性[J].南京医科大学学报(自然科学版),2020,(1):72-76

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  • 收稿日期:2018-12-06
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  • 在线发布日期: 2020-02-09
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