Intrauterine exposure to hyperglycaemia may increase the risk of later-life metabolic disorders. Although the underlying mechanism is not fully understood, epigenetic dysregulation in fetal programming has been implicated. With regard to energy homoeostasis, PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α, encoded by the PPARGC1A gene) plays a regulatory role in several biochemical processes. We hypothesized that maternal gestational glucose levels would positively correlate with DNA methylation of the PPARGC1A promoter in placental tissue. We undertook a cross-sectional study of 58 mothers who underwent uncomplicated Caesarean delivery in a university hospital. Maternal gestational glucose concentration was determined after a 75-g OGTT (oral glucose tolerance test) at 24–28 weeks of gestation. Placenta tissue and cord blood were collected immediately after delivery. Genomic DNA was extracted and thereafter bisulfite conversion was performed. After PCR amplification, the DNA methylation of the PPARGC1A promoter was quantified using a pyrosequencing technique. The protein level of PGC-1α was evaluated by Western blotting. For all participants as a whole, including the GDM (gestational diabetes mellitus) and normoglycaemia groups, the maternal gestational glucose level was positively correlated with placental DNA methylation, and negatively correlated with cord blood DNA methylation of the PPARGC1A promoter in a CpG site-specific manner. In the GDM group alone, the placental CpG site-specific methylation of the PPARGC1A promoter strongly correlated with gestational 2-h post-OGTT glycaemia. Epigenetic alteration of the PPAGRC1A promoter may be one of the potential mechanisms underlying the metabolic programming in offspring exposed to intrauterine hyperglycaemia.
Placental DNA methylation of peroxisome-proliferator-activated receptor-γ co-activator-1α promoter is associated with maternal gestational glucose level
Xuemei Xie, Hongjie Gao, Wanjiang Zeng, Suhua Chen, Ling Feng, Dongrui Deng, Fu-yuan Qiao, Lihong Liao, Kenneth McCormick, Qin Ning, Xiaoping Luo; Placental DNA methylation of peroxisome-proliferator-activated receptor-γ co-activator-1α promoter is associated with maternal gestational glucose level. Clin Sci (Lond) 1 August 2015; 129 (4): 385–394. doi: https://doi.org/10.1042/CS20140688
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