title: Seeking genes responsible for developmental origins of health and disease from the fetal mouse liver following maternal food restriction.
abstract: Low birthweight resulting from a non-optimal fetal environment is correlated epidemiologically to a higher risk of adult diseases, and which has also been demonstrated using animal models for maternal undernutrition. In this study, we subjected pregnant mice to 50% food restriction (FR), and profiled gene expression and promoter DNA methylation genome-wide using the fetal livers. The fact that effect of food restriction is opposite between before and after birth encouraged us to hunt for genes that are expressed oppositely to adult calorie restriction (CR) using the maternal livers. Among oppositely regulated genes, we identified trib1 (tribbles homolog 1). Using genetically modified mice, trib1 has been shown to have a demonstrable contribution to a risk of hypertriglyceridaemia and insulin resistance. Our data showed that the trib1 expression and its promoter DNA methylation could be affected physiologically (by maternal nutrition), and therefore might be a strong candidate gene for developmental origins of adult diseases. Furthermore, lepr (leptin receptor) gene was downregulated by maternal FR, indicating its potential role in induction of obesity and diabetes. Gene expression as well as promoter DNA methylation profiling revealed that glucocorticoid receptor target genes were regulated by maternal FR. This supports previous studies that suggest an important role of fetal glucocorticoid exposure in the mechanism of developmental origins of diseases. Our transcriptomics profiling data also suggested that maternal FR impaired development of the immune system. An inventory of candidate genes responsible for developmental origins of health and disease is presented and discussed in this study.
authors.affiliation: Department of Anatomy, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ogawa
authors.forename: Junko
authors.initials: J
authors.lastname: Shibato
authors.forename: Randeep
authors.initials: R
authors.lastname: Rakwal
authors.forename: Tomomi
authors.initials: T
authors.lastname: Saito
authors.forename: Gaku
authors.initials: G
authors.lastname: Tamura
authors.forename: Makiko
authors.initials: M
authors.lastname: Kuwagata
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
mesh_terms: D000328:Adult; D000818:Animals; D031204:Caloric Restriction; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D005333:Fetus; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008431:Maternal-Fetal Exchange / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D054411:Receptors, Leptin / Q000096:biosynthesis*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D054411:Receptors, Leptin; C523598:Trib1 protein, mouse; C515447:leptin receptor, mouse; D017346:Protein Serine-Threonine Kinases
keywords: developmental origins of health and disease; lepr; maternal undernutrition; promoter methylation microarray; trib1