Variation of DNA methylation in candidate age-related targets on the mitochondrial-telomere axis in cord blood and placenta

• Published in: Placenta (Eastbourne) 2014-09, Vol.35 (9), p.665-672
• Main Authors: Janssen, B.G, Byun, H.M, Cox, B, Gyselaers, W, Izzi, B, Baccarelli, A.A, Nawrot, T.S
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Ageing; Aging - metabolism; Biological and medical sciences; Cohort Studies; Concordance; Cord blood; DNA Methylation; Embryology: invertebrates and vertebrates. Teratology; Epigenetics; Female; Fetal Blood - chemistry; Fundamental and applied biological sciences. Psychology; Genome, Mitochondrial; Humans; Internal Medicine; Obstetrics and Gynecology; Placenta; Placenta - metabolism; Pregnancy; Promoter Regions, Genetic; Telomere - metabolism; Within-placenta variation; Young Adult
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2014.06.371

Abstract Background Epigenetics is tissue-specific and potentially even cell-specific, but little information is available from human reproductive studies about the concordance of DNA methylation patterns in cord blood and placenta, as well as within-placenta variations. We evaluated methylation levels at promoter regions of candidate genes in biological ageing pathways ( SIRT1, TP53, PPARG, PPARGC1A , and TFAM ), a subtelomeric region ( D4Z4 ) and the mitochondrial genome ( MT-RNR1, D-loop ). Methods Ninety individuals were randomly chosen from the ENVIR ON AGE birth cohort to evaluate methylation concordance between cord blood and placenta using highly quantitative bisulfite-PCR pyrosequencing. In a subset of nineteen individuals, a more extensive sampling scheme was performed to examine within-placenta variation. Results The DNA methylation levels of the subtelomeric region and mitochondrial genome showed concordance between cord blood and placenta with correlation coefficients ranging from r  = 0.31 to 0.43, p  ≤ 0.005, and also between the maternal and foetal sides of placental tissue ( r  = 0.53 to 0.72, p  ≤ 0.05). For the majority of targets, an agreement in methylation levels between four foetal biopsies was found (with intra-class correlation coefficients ranging from 0.16 to 0.72), indicating small within-placenta variation. Conclusions The methylation levels of the subtelomeric region ( D4Z4) and mitochondrial genome ( MT-RNR1 , D-loop ) showed concordance between cord blood and placenta, suggesting a common epigenetic signature of these targets between tissues. Concordance was lacking between the other genes that were studied. In placental tissue, methylation patterns of most targets on the mitochondrial-telomere axis were not strongly influenced by sample location.