title: Increased epigenetic alterations at the promoters of transcriptional regulators following inadequate maternal gestational weight gain.
abstract: 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.
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Abe
authors.affiliation: Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Okamura
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kamura
authors.affiliation: Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Rina
authors.initials: R
authors.lastname: Akaishi
authors.affiliation: Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Minakami
authors.affiliation: Division of Developmental Genomics, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hata
mesh_terms: D001724:Birth Weight; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000473:pathology; D005333:Fetus; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D063990:Gene Ontology; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058977:Molecular Sequence Annotation; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D015430:Weight Gain / Q000235:genetics*
chemical_list: C112743:FOXC1 protein, human; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; C490538:HOXB7 protein, human; D018398:Homeodomain Proteins