An obesogenic diet during mouse pregnancy modifies maternal nutrient partitioning and the fetal growth trajectory.

In developed societies, high-sugar and high-fat (HSHF) diets are now the norm and are increasing the rates of maternal obesity during pregnancy. In pregnant rodents, these diets lead to cardiovascular and metabolic dysfunction in their adult offspring, but the intrauterine mechanisms involved remain unknown. This study shows that, relative to standard chow, HSHF feeding throughout mouse pregnancy increases maternal adiposity (+30%, P<0.05) and reduces fetoplacental growth at d 16 (-10%, P<0.001). At d 19, however, HSHF diet group pup weight had normalized, despite the HSHF diet group placenta remaining small and morphologically compromised. This altered fetal growth trajectory was associated with enhanced placental glucose and amino acid transfer (+35%, P<0.001) and expression of their transporters (+40%, P<0.024). HSHF feeding also up-regulated placental expression of fatty acid transporter protein, metabolic signaling pathways (phosphoinositol 3-kinase and mitogen-activated protein kinase), and several growth regulatory imprinted genes (Igf2, Dlk1, Snrpn, Grb10, and H19) independently of changes in DNA methylation. Obesogenic diets during pregnancy, therefore, alter maternal nutrient partitioning, partly through changes in the placental phenotype, which helps to meet fetal nutrient demands for growth near term. However, by altering provision of specific nutrients, dietary-induced placental adaptations have important roles in programming development with health implications for the offspring in later life.

The science of hope: an interview with Randy Jirtle.

In this interview, Professor Randy L Jirtle speaks with Storm Johnson, Commissioning Editor for Epigenomics, on his work on genomic imprinting, environmental epigenomics and the fetal origins of disease susceptibility. Professor Randy Jirtle joined the Duke University Department of Radiology in 1977 and headed the Epigenetics and Imprinting Laboratory until 2012. He is now Professor of Epigenetics in the Department of Biological Sciences at North Carolina State University, Raleigh, NC, USA. Jirtle's research interests are in epigenetics, genomic imprinting and the fetal origins of disease susceptibility. He is known for his groundbreaking studies linking environmental exposures early in life to the development of adult diseases through changes in the epigenome and for determining the evolutionary origin of genomic imprinting in mammals. He has published over 200 peer-reviewed articles as well as the books Liver Regeneration andCarcinogenesis: Molecular and Cellular Mechanisms, Environmental Epigenomics in Health and Disease: Epigenetics and Disease Origins and Environmental Epigenomics in Health andDisease: Epigenetics and Complex Diseases. He was honored in 2006 with the Distinguished Achievement Award from the College of Engineering at the University of Wisconsin-Madison. In 2007, he was a featured scientist on the NOVA television program on epigenetics titled 'Ghost in Your Genes' and was nominated for Time Magazine's 'Person of the Year'. He was the inaugural recipient of the Epigenetic Medicine Award in 2008 and received the STARS Lecture Award in Nutrition and Cancer from the National Cancer Institute in 2009. Jirtle was presented the Linus Pauling Award from the Institute of Functional Medicine in 2014. In 2017, ShortCutsTV produced the English documentary 'Are You What Your Mother Ate? The Agouti Mouse Study' based on his pioneering epigenetic research. He received the 2018 Northern Communities Health Foundation Visiting Professorship Award at the University of Adelaide, Australia. The Personalized Lifestyle Medicine Institute presented Jirtle with the Research and Innovation Leadership Award in 2019. Dr Jirtle was also given the Alexander Hollaender Award in 2019 at the 50th annual meeting of the Environmental Mutagenesis and Genomics Society.

Genomic Imprinting in the New Omics Era: A Model for Systems-Level Approaches.

Genomic imprinting represents a noteworthy inheritance mechanism leading to allele-specific regulations dependent of the parental origin. Imprinted loci are especially involved in essential mammalian functions related to growth, development and behavior. In this mini-review, we first offer a summary of current representations associated with genomic imprinting through key results of the three last decades. We then outline new perspectives allowed by the spread of new omics technologies tackling various interacting levels of imprinting regulations, including genomics, transcriptomics and epigenomics. We finally discuss the expected contribution of new omics data to unresolved big questions in the field.

The human imprintome: regulatory mechanisms, methods of ascertainment, and roles in disease susceptibility.

Imprinted genes form a special subset of the genome, exhibiting monoallelic expression in a parent-of-origin-dependent fashion. This monoallelic expression is controlled by parental-specific epigenetic marks, which are established in gametogenesis and early embryonic development and are persistent in all somatic cells throughout life. We define this specific set of cis-acting epigenetic regulatory elements as the imprintome, a distinct and specially tasked subset of the epigenome. Imprintome elements contain DNA methylation and histone modifications that regulate monoallelic expression by affecting promoter accessibility, chromatin structure, and chromatin configuration. Understanding their regulation is critical because a significant proportion of human imprinted genes are implicated in complex diseases. Significant species variation in the repertoire of imprinted genes and their epigenetic regulation, however, will not allow model organisms solely to be used for this crucial purpose. Ultimately, only the human will suffice to accurately define the human imprintome.