DNA methylation in promoter regions of genes involved in the reproductive and metabolic function of children born to women with PCOS
- 1 November 2020
- journal article
- research article
- Published by Taylor & Francis Ltd in Epigenetics
- Vol. 15 (11), 1178-1194
- https://doi.org/10.1080/15592294.2020.1754674
Abstract
Clinical and experimental evidences indicate that epigenetic modifications induced by the prenatal environment are related to metabolic and reproductive derangements in polycystic ovary syndrome (PCOS). Alterations in the leptin and adiponectin systems, androgen signalling and antimullerian hormone (AMH) levels have been observed in PCOS women and in their offspring. Using a targeted Next-Generation Sequencing (NGS), we studied DNA methylation in promoter regions of the leptin (LEP), leptin receptor (LEPR), adiponectin (ADIPOQ), adiponectin receptor 1 and 2 (ADIPOR1 and ADIPOR2), AMH and androgen receptor (AR) genes in 24 sons and daughters of women with PCOS (12 treated with metformin during pregnancy) and 24 children born to non-PCOS women during early infancy (2-3 months of age). Genomic DNA was extracted from whole blood, bisulphite converted and sequenced by NGS. Girls showed differences between groups in 1 CpG site of LEPR, 2 of LEP, 1 of ADIPOR2 and 2 of AR. Boys showed differences in 5 CpG sites of LEP, 3 of AMH and 9 of AR. Maternal metformin treatment prevented some of these changes in LEP, ADIPOR2 and partially in AR in girls, and in LEP and AMH in boys. Maternal BMI at early pregnancy was inversely correlated with the methylation levels of the ChrX-67544981 site in the whole group of girls (r = -0.530, p = 0.008) and with the global Z-score in all boys (r = -0.539, p = 0.007). These data indicate that the intrauterine PCOS environment predisposes the offspring to acquire certain sex-dependent DNA methylation patterns in the promoter regions of metabolic and reproductive genes.Funding Information
- Fondo Nacional de Desarrollo Científico y Tecnológico (National Fund for Scientific and Technological Research) FONDECYT (1151531)
- VID research travelling support grant of the University of Chile (UCH-1566)
- Fondo Nacional de Desarrollo Científico y Tecnológico (National Fund for Scientific and Technological Research) FONDECYT (1181798)
This publication has 93 references indexed in Scilit:
- Identification and systematic annotation of tissue-specific differentially methylated regions using the Illumina 450k arrayEpigenetics & Chromatin, 2013
- Fetal epigenetic programming of adipokinesAdipocyte, 2013
- Functions of DNA methylation: islands, start sites, gene bodies and beyondNature Reviews Genetics, 2012
- Environmentally induced epigenetic transgenerational inheritance of phenotype and diseaseMolecular and Cellular Endocrinology, 2012
- Krüppel-like factor 4 regulates macrophage polarizationJCI Insight, 2011
- Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applicationsBioinformatics, 2011
- DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specificHuman Molecular Genetics, 2009
- Genome-scale DNA methylation maps of pluripotent and differentiated cellsNature, 2008
- Differential Recruitment of Methylated CpG Binding Domains by the Orphan Receptor GCNF Initiates the Repression and Silencing of Oct4 ExpressionMolecular and Cellular Biology, 2006
- DNA methylation patterns and epigenetic memoryGenes & Development, 2002