DNA Methylation Reorganization of Skeletal Muscle-Specific Genes in Response to Gestational Obesity

Frontiers in Physiology

卷:11

Judit Bassols¹  Sergi García-Retortillo²  Fidanka Vasileva³  Abel López-Bermejo⁴  Berta Mas-Parés⁴  Sílvia Xargay-Torrent⁵  Gemma Carreras-Badosa⁵  Anna Prats-Puig⁶  Raquel Font-Lladó⁶  Miquel Puig-Parnau⁶ 

[1] Fetal Metabolic Research, Girona Institute for Biomedical Research, Salt, Spain;

[2] Complex Systems in Sport, National Institute of Physical Education and Sport of Catalonia (INEFC), Universitat de Barcelona (UB), Barcelona, Spain;

[3] Faculty of Physical Education, Sport and Health, Ss. Cyril and Methodius University, Skopje, North Macedonia;

[4] Maternal &

[5] Pediatric Endocrinology, Girona Institute for Biomedical Research, Dr. Josep Trueta Hospital, Girona, Spain;

[6] University School of Health and Sport (EUSES), University of Girona, Girona, Spain;

关键词: gestational obesity;    skeletal muscle;    umbilical cord tissue;    methylation;    network physiology;   

DOI  :  10.3389/fphys.2020.00938

来源: DOAJ

【 摘 要 】

The goals were to investigate in umbilical cord tissue if gestational obesity: (1) was associated with changes in DNA methylation of skeletal muscle-specific genes; (2) could modulate the co-methylation interactions among these genes. Additionally, we assessed the associations between DNA methylation levels and infant’s variables at birth and at age 6. DNA methylation was measured in sixteen pregnant women [8-gestational obesity group; 8-control group] in umbilical cord using the Infinium Methylation EPIC Bead Chip microarray. Differentially methylated CpGs were identified with Beta Regression Models [false discovery rate (FDR) < 0.05 and an Odds Ratio > 1.5 or < 0.67]. DNA methylation interactions between CpGs of skeletal muscle-specific genes were studied using data from Pearson correlation matrices. In order to quantify the interactions within each network, the number of links was computed. This identification analysis reported 38 differential methylated CpGs within skeletal muscle-specific genes (comprising 4 categories: contractibility, structure, myokines, and myogenesis). Compared to control group, gestational obesity (1) promotes hypermethylation in highly methylated genes and hypomethylation in low methylated genes; (2) CpGs in regions close to transcription sites and with high CpG density are hypomethylated while regions distant to transcriptions sites and with low CpG density are hypermethylated; (3) diminishes the number of total interactions in the co-methylation network. Interestingly, the associations between infant’s fasting glucose at age 6 and MYL6, MYH11, TNNT3, TPM2, CXCL2, and NCAM1 were still relevant after correcting for multiple testing. In conclusion, our study showed a complex interaction between gestational obesity and the epigenetic status of muscle-specific genes in umbilical cord tissue. Additionally, gestational obesity may alter the functional co-methylation connectivity of CpG within skeletal muscle-specific genes interactions, our results revealing an extensive reorganization of methylation in response to maternal overweight. Finally, changes in methylation levels of skeletal muscle specific genes may have persistent effects on the offspring of mothers with gestational obesity.

【 授权许可】

Unknown