title: Placental DNA methylation of peroxisome-proliferator-activated receptor-γ co-activator-1α promoter is associated with maternal gestational glucose level.
abstract: 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.
authors: *Department of Pediatrics Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Xuemei
authors: X
authors: Xie
authors: *Department of Pediatrics Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Hongjie
authors: H
authors: Gao
authors: ‡Department of Obstetrics and Gynaecology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Wanjiang
authors: W
authors: Zeng
authors: ‡Department of Obstetrics and Gynaecology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Suhua
authors: S
authors: Chen
authors: ‡Department of Obstetrics and Gynaecology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Ling
authors: L
authors: Feng
authors: ‡Department of Obstetrics and Gynaecology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Dongrui
authors: D
authors: Deng
authors: ‡Department of Obstetrics and Gynaecology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Fu-yuan
authors: FY
authors: Qiao
authors: *Department of Pediatrics Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Lihong
authors: L
authors: Liao
authors: †Department of Pediatrics, Division of Endocrinology, University of Alabama at Birmingham, Birmingham, AL 35233, U.S.A.
authors: Kenneth
authors: K
authors: McCormick
authors: §Department of Infectious Diseases Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Qin
authors: Q
authors: Ning
authors: *Department of Pediatrics Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Xiaoping
authors: X
authors: Luo
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D018899:CpG Islands; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D016640:Diabetes, Gestational / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D004734:Energy Metabolism; D044127:Epigenesis, Genetic; D005260:Female; D005865:Gestational Age; D006801:Humans; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors