title: Diabetic embryopathy: a role for the epigenome?
abstract: Embryonic development under adverse conditions, such as maternal diabetes or obesity during pregnancy, constitutes a major risk factor for birth defects, as well as for long-term health consequences and disease susceptibility in the offspring. While contributions from epigenetic changes have been invoked previously to explain the long-term changes in terms of developmental programming, we here review how maternal metabolism may directly affect the embryonic epigenome in relationship to teratogenic processes. We consider four epigenetic modalities--DNA methylation, non-coding RNA, transcription factors, and histone modifications--and their contribution to epigenetic memory, and discuss how epigenomic changes may mediate the altered control of embryonic gene expression brought about by maternal diabetes. In combination, the epigenomic modalities serve to define transcription-permissive domains of the genome, resulting in distinct epigenomic landscapes in different developmental cell types. We evaluate experimental approaches to characterize the epigenome in adverse pregnancy conditions, highlighting the role of next-generation sequencing on the technological side, while emphasizing the necessity to study defined cell populations in terms of biologic impact. Finally, we outline the challenges in moving from findings that correlate epigenomics to developmental phenotypes to scenarios that establish teratogenic causality.
authors.affiliation: Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA. michael.salbaum@pbrc.edu
authors.forename: J Michael
authors.initials: JM
authors.lastname: Salbaum
authors.forename: Claudia
authors.initials: C
authors.lastname: Kappen
mesh_terms: D000818:Animals; D016640:Diabetes, Gestational; D004198:Disease Susceptibility; D004622:Embryo, Mammalian / Q000473:pathology*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D011247:Pregnancy; D011254:Pregnancy in Diabetics