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

被引:10
作者
Garcia-Gomez, Elizabeth [1 ]
Gomez-Viais, Yadira Ines [2 ]
Cruz-Aranda, Martin Mizael [2 ]
Martinez-Razo, Luis Daniel [2 ]
Reyes-Mayoral, Christian [3 ]
Ibarra-Gonzalez, Lizeth [4 ]
Montoya-Estrada, Araceli [5 ]
Osorio-Caballero, Mauricio [6 ]
Perichart-Perera, Otilia [4 ]
Camacho-Arroyo, Ignacio [2 ]
Cerbon, Marco [2 ]
Reyes-Munoz, Enrique [5 ]
Vazquez-Martinez, Edgar Ricardo [2 ]
机构
[1] Univ Nacl Autonoma Mexico, Fac Quim, Consejo Nacl Ciencia & Tecnol CONACYT, Unidad Invest Reprod Humana,Inst Nacl Perinatol I, Mexico City 11000, DF, Mexico
[2] Univ Nacl Autonoma Mexico, Fac Quim, Unidad Invest Reprod Humana, Inst Nacl Perinatol INPer, Mexico City 11000, DF, Mexico
[3] Clin Estudio Reprod Humana CERH Bajio, Irapuato 36650, Mexico
[4] Inst Nacl Perinatol INPer, Dept Nutr & Bioprogramac, Mexico City 11000, DF, Mexico
[5] Inst Nacl Perinatol INPer, Coordinac Endocrinol Ginecol & Perinatal, Mexico City 11000, DF, Mexico
[6] Inst Nacl Perinatol INPer, Dept Salud Sexual & Reprod, Mexico City 11000, DF, Mexico
关键词
polycystic ovary syndrome; endometrium; DNA methylation; gene expression; metformin; dietary intervention; insulin pathway; endometrial receptivity; PROMOTER METHYLATION; ESTROGEN-RECEPTORS; STEROID-RECEPTORS; MENSTRUAL-CYCLE; CELL-MIGRATION; HOXA10; MOLECULES; IMPLANTATION; COREGULATORS; RECEPTIVITY;
D O I
10.3390/ijms24076857
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 HOXA10, GAB1, and SLC2A4 genes and increased DNA methylation levels of the HOXA10 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 HOXA10, ESR1, GAB1, and SLC2A4 genes and reduced DNA methylation levels of the HOXA10 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 HOXA10 gene promoter and the expression of genes implicated in endometrial receptivity and insulin signaling.
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页数:16
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