Increased epigenetic alterations at the promoters of transcriptional regulators following inadequate maternal gestational weight gain

• Published in: Scientific reports Vol. 5; no. 1; p. 14224
• Main Authors: Kawai, Tomoko, Yamada, Takahiro, Abe, Kosei, Okamura, Kohji, Kamura, Hiromi, Akaishi, Rina, Minakami, Hisanori, Nakabayashi, Kazuhiko, Hata, Kenichiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29-09-2015; Nature Publishing Group
• Subjects: 631/337/176/1988; 631/443; Birth Weight; Case-Control Studies; Chromatin; CpG Islands; DNA Methylation; Epigenesis, Genetic; Epigenetics; Female; Fetal Growth Retardation - genetics; Fetal Growth Retardation - pathology; Fetus; Forkhead Box Protein L2; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene Ontology; Genetic Loci; Genome-Wide Association Study; Genomes; Gestational Age; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humanities and Social Sciences; Humans; Intrauterine exposure; Mental disorders; Molecular Sequence Annotation; multidisciplinary; Offspring; Placenta; Placenta - metabolism; Polycomb group proteins; Postpartum; Pregnancy; Prenatal Exposure Delayed Effects - genetics; Prenatal Exposure Delayed Effects - pathology; Promoter Regions, Genetic; Promoters; Science; Transcription; Weight Gain - genetics; Zinc finger proteins
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep14224

Epigenetic modifications are thought to serve as a memory of exposure to
in utero
environments. However, few human studies have investigated the associations between maternal nutritional conditions during pregnancy and epigenetic alterations in offspring. In this study, we report genome-wide methylation profiles for 33 postpartum placentas from pregnancies of normal and foetal growth restriction with various extents of maternal gestational weight gain. Epigenetic alterations accumulate in the placenta under adverse
in utero
environments, as shown by application of Smirnov-Grubbs’ outlier test. Moreover, hypermethylation occurs frequently at the promoter regions of transcriptional regulator genes, including polycomb targets and zinc-finger genes, as shown by annotations of the genomic and functional features of loci with altered DNA methylation. Aberrant epigenetic modifications at such developmental regulator loci, if occurring in foetuses as well, will elevate the risk of developing various diseases, including metabolic and mental disorders, later in life.