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二甲双胍和碳水化合物控制饮食对多囊卵巢综合征妇女子宫内膜 DNA 甲基化和基因表达的影响。

The Effect of Metformin and Carbohydrate-Controlled Diet on DNA Methylation and Gene Expression in the Endometrium of Women with Polycystic Ovary Syndrome.

机构信息

Consejo Nacional de Ciencia y Tecnología (CONACYT)-Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología (INPer)-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City 11000, Mexico.

Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología (INPer)-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City 11000, Mexico.

出版信息

Int J Mol Sci. 2023 Apr 6;24(7):6857. doi: 10.3390/ijms24076857.

DOI:10.3390/ijms24076857
PMID:37047828
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10094785/
Abstract

Polycystic ovary syndrome (PCOS) is an endocrine disease associated with infertility and metabolic disorders in reproductive-aged women. In this study, we evaluated the expression of eight genes related to endometrial function and their DNA methylation levels in the endometrium of PCOS patients and women without the disease (control group). In addition, eight of the PCOS patients underwent intervention with metformin (1500 mg/day) and a carbohydrate-controlled diet (type and quantity) for three months. Clinical and metabolic parameters were determined, and RT-qPCR and MeDIP-qPCR were used to evaluate gene expression and DNA methylation levels, respectively. Decreased expression levels of , , and genes and increased DNA methylation levels of the promoter were found in the endometrium of PCOS patients compared to controls. After metformin and nutritional intervention, some metabolic and clinical variables improved in PCOS patients. This intervention was associated with increased expression of , , and genes and reduced DNA methylation levels of the promoter in the endometrium of PCOS women. Our preliminary findings suggest that metformin and a carbohydrate-controlled diet improve endometrial function in PCOS patients, partly by modulating DNA methylation of the gene promoter and the expression of genes implicated in endometrial receptivity and insulin signaling.

摘要

多囊卵巢综合征（PCOS）是一种与生殖期妇女不孕和代谢紊乱相关的内分泌疾病。在本研究中，我们评估了 PCOS 患者和无该病女性（对照组）子宫内膜中与子宫内膜功能相关的 8 个基因的表达及其 DNA 甲基化水平。此外，8 名 PCOS 患者接受了二甲双胍（1500mg/天）和碳水化合物控制饮食（种类和数量）干预治疗三个月。测定了临床和代谢参数，并分别采用 RT-qPCR 和 MeDIP-qPCR 评估基因表达和 DNA 甲基化水平。与对照组相比，PCOS 患者的子宫内膜中 、 、 和 基因的表达水平降低， 启动子的 DNA 甲基化水平升高。在 PCOS 患者中，经过二甲双胍和营养干预后，一些代谢和临床变量得到改善。这种干预与 PCOS 女性子宫内膜中 、 、 和 基因的表达增加以及 启动子的 DNA 甲基化水平降低有关。我们的初步研究结果表明，二甲双胍和碳水化合物控制饮食通过调节 基因启动子的 DNA 甲基化和参与子宫内膜容受性和胰岛素信号的基因表达，改善了 PCOS 患者的子宫内膜功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/651a/10094785/542370f59e36/ijms-24-06857-g004.jpg
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