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妊娠期糖尿病孕妇胎盘维生素 D 及其相关基因的表达。

Placenta expression of vitamin D and related genes in pregnant women with gestational diabetes mellitus.

机构信息

Department of Obstetrics & Gynecology, Hebei General Hospital, Shijiazhuang 050051, China.

Department of Obstetrics & Gynecology, Hebei General Hospital, Shijiazhuang 050051, China.

出版信息

J Steroid Biochem Mol Biol. 2020 Nov;204:105754. doi: 10.1016/j.jsbmb.2020.105754. Epub 2020 Sep 15.

DOI:10.1016/j.jsbmb.2020.105754
PMID:32946925
Abstract

OBJECTIVES AND METHODS

A total of 41 GDM and 40 normal glucose tolerance subjects were recruited. Through detecting the level of Serum vitamin D with electrochemical luminescence and vitamin D receptor (VDR) with Enzyme-linked immunosorbent assay (ELISA) in maternal and cord blood, the expression leves of CYP24A1, CYP27B1, VDR protein and mRNA in placenta and umbilical cord with western blotting and RT-PCR, and the DNA methylation levels of CYP24A1 and CYP27B1 gene in placenta with methylation-specific PCR (MSP) and direct bisulfite sequencing (BSP) analysis to explore the potential role of the vitamin D and its related genes in gestational diabetes mellitus (GDM).

RESULTS

Serum vitamin D concentrations were significantly higher in normal pregnant than women with GDM in maternal blood (P < 0.01) and cord blood (P = 0.014). Compared to the control group, the expression levels of CYP24A1 protein (P < 0.01) and mRNA (P = 0.021) and VDR protein (P = 0.026) and mRNA (P = 0.023) in the GDM group were significantly higher in placenta and umbilical cord tissues (P = 0.015, P < 0.01, P = 0.028, P < 0.01, respectively), while that of CYP27B1 protein (P < 0.01) and mRNA (P = 0.042) was significantly lower (P = 0.022, P = 0.032, respectively). Moreover, partial DNA methylation of CYP24A1 and CYP27B1 genes was observed in both GDM and control groups.

CONCLUSIONS

Vitamin D deficiency participates in the pathogenesis of GDM, and changes in the expression of genes related to the vitamin D metabolic pathway are closely related to vitamin D levels in the pregnancy and fetus. However, DNA methylation of CYP24A1 and CYP27B1 might not be involved in the pathogenesis of GDM.

摘要

目的和方法

共招募了 41 例 GDM 患者和 40 例糖耐量正常的孕妇。通过电化学发光法检测母血和脐血中血清维生素 D 水平,酶联免疫吸附试验(ELISA)检测维生素 D 受体(VDR)水平,采用 Western blot 和 RT-PCR 检测胎盘和脐带组织中 CYP24A1、CYP27B1、VDR 蛋白和 mRNA 的表达水平,采用甲基化特异性 PCR(MSP)和直接亚硫酸氢盐测序(BSP)分析胎盘 CYP24A1 和 CYP27B1 基因的 DNA 甲基化水平,探讨维生素 D 及其相关基因在妊娠期糖尿病(GDM)发病机制中的作用。

结果

母血(P < 0.01)和脐血(P = 0.014)中 GDM 患者的血清维生素 D 浓度明显低于正常孕妇。与对照组相比,GDM 组胎盘和脐带组织中 CYP24A1 蛋白(P < 0.01)和 mRNA(P = 0.021)以及 VDR 蛋白(P = 0.026)和 mRNA(P = 0.023)的表达水平均明显升高(P = 0.015、P < 0.01、P = 0.028、P < 0.01),而 CYP27B1 蛋白(P < 0.01)和 mRNA(P = 0.042)的表达水平则明显降低(P = 0.022、P = 0.032)。此外,GDM 组和对照组均观察到 CYP24A1 和 CYP27B1 基因的部分 DNA 甲基化。

结论

维生素 D 缺乏参与了 GDM 的发病机制,维生素 D 代谢途径相关基因的表达变化与孕妇和胎儿的维生素 D 水平密切相关。然而,CYP24A1 和 CYP27B1 基因的 DNA 甲基化可能与 GDM 的发病机制无关。

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