title: Early origins of adult disease: approaches for investigating the programmable epigenome in humans, nonhuman primates, and rodents.
abstract: According to the developmental origins of health and disease hypothesis, in utero experiences reprogram an individual for immediate adaptation to gestational perturbations, with the sequelae of later-in-life risk of metabolic disease. An altered gestational milieu with resultant adult metabolic disease has been observed in instances of both in utero constraint (e.g., from famine or uteroplacental insufficiency) and overt caloric abundance (e.g., from a maternal high-fat, caloric-dense diet). The commonality of the adult metabolic phenotype begs the question of how diverse in utero experiences (i.e., reprogramming events) converge on common metabolic pathways and how the memory of these events is maintained across the lifespan. We and others have investigated the molecular mechanisms underlying fetal programming and observed that epigenetic modifications to the fetal and placental epigenome accompany these reprogramming events. Based on several lines of emerging data in human and nonhuman primates, it is now felt that modified epigenetic signature--and the histone code in particular--underlies alterations in postnatal gene expression and metabolic pathways central to accurate functioning and maintenance of health. Because of the tissue lineage specificity of many of these modifications, nonhuman primates serve as an apt model system for the capacity to recapitulate human gene expression and regulation during development. This review summarizes recent epigenetic advances using rodent and primate (both human and nonhuman) models during in utero development and contributing to adult diseases later in life.
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Radhika S
authors.initials: RS
authors.lastname: Ganu
authors.forename: R Alan
authors.initials: RA
authors.lastname: Harris
authors.forename: Kiara
authors.initials: K
authors.lastname: Collins
authors.forename: Kjersti M
authors.initials: KM
authors.lastname: Aagaard
mesh_terms: D000818:Animals; D044127:Epigenesis, Genetic / Q000235:genetics*; D057890:Epigenomics; D005260:Female; D047109:Fetal Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D006801:Humans; D011247:Pregnancy; D011323:Primates; D012377:Rodentia
keywords: behavioral epigenetics; developmental origins of health and disease (DOHaD); environmental epigenetics; microbiome; nonhuman primate (NHP)