Newborns of obese parents have altered DNA methylation patterns at imprinted genes.

Abstract

Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity.We examined parental preconceptional obesity in relation to DNA methylation profiles at multiple human imprinted genes important in normal growth and development, such as: maternally expressed gene 3 (MEG3), mesoderm-specific transcript (MEST), paternally expressed gene 3 (PEG3), pleiomorphic adenoma gene-like 1 (PLAGL1), epsilon sarcoglycan and paternally expressed gene 10 (SGCE/PEG10) and neuronatin (NNAT).We measured methylation percentages at the differentially methylated regions (DMRs) by bisulfite pyrosequencing in DNA extracted from umbilical cord blood leukocytes of 92 newborns. Preconceptional obesity, defined as BMI ⩾30 kg m(-2), was ascertained through standardized questionnaires.After adjusting for potential confounders and cluster effects, paternal obesity was significantly associated with lower methylation levels at the MEST (β=-2.57; s.e.=0.95; P=0.008), PEG3 (β=-1.71; s.e.=0.61; P=0.005) and NNAT (β=-3.59; s.e.=1.76; P=0.04) DMRs. Changes related to maternal obesity detected at other loci were as follows: β-coefficient was +2.58 (s.e.=1.00; P=0.01) at the PLAGL1 DMR and -3.42 (s.e.=1.69; P=0.04) at the MEG3 DMR.We found altered methylation outcomes at multiple imprint regulatory regions in children born to obese parents, compared with children born to non-obese parents. In spite of the small sample size, our data suggest a preconceptional influence of parental life-style or overnutrition on the (re)programming of imprint marks during gametogenesis and early development. More specifically, the significant and independent association between paternal obesity and the offspring's methylation status suggests the susceptibility of the developing sperm for environmental insults. The acquired imprint instability may be carried onto the next generation and increase the risk for chronic diseases in adulthood.

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Published Version (Please cite this version)

10.1038/ijo.2013.193

Publication Info

Soubry, A, SK Murphy, F Wang, Z Huang, AC Vidal, BF Fuemmeler, J Kurtzberg, A Murtha, et al. (2015). Newborns of obese parents have altered DNA methylation patterns at imprinted genes. International journal of obesity (2005), 39(4). pp. 650–657. 10.1038/ijo.2013.193 Retrieved from https://hdl.handle.net/10161/20701.

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Scholars@Duke

Murphy

Susan Kay Murphy

Associate Professor in Obstetrics and Gynecology

Dr. Murphy is a tenured Associate Professor in the Department of Obstetrics and Gynecology and serves as Chief of the Division of Reproductive Sciences. As a molecular biologist with training in human epigenetics, her research interests are largely centered around the role of epigenetic modifications in health and disease. 

Dr. Murphy has ongoing projects on gynecologic malignancies, including approaches to eradicate ovarian cancer cells that survive chemotherapy and later give rise to recurrent disease. Dr. Murphy is actively involved in many collaborative projects relating to the Developmental Origins of Health and Disease (DOHaD).

Her lab is currently working on preconception environmental exposures in males, particularly on the impact of cannabis on the sperm epigenome and the potential heritability of these effects. They are also studying the epigenetic and health effects of in utero exposures, with primary focus on children from the Newborn Epigenetics STudy (NEST), a pregnancy cohort she co-founded who were recruited from central North Carolina between 2005 and 2011. Dr. Murphy and her colleagues continue to follow NEST children to determine relationships between prenatal exposures and later health outcomes.

Huang

Zhiqing Huang

Assistant Professor in Obstetrics and Gynecology

Dr. Huang is an Assistant Professor in the Department of Obstetrics and Gynecology, Division of Reproductive Sciences, at Duke University Medical Center. She obtained her MD at North China Coal Medical University in China and her PhD at the University of Heidelberg in Germany under the mentorship of Dr. Ralph Witzgall. She did her postdoctoral training with Dr. Jiemin Wong at Baylor College of Medicine, studying how histone methylation and chromatin modifications regulate androgen receptor transcription. 

Dr. Huang’s research includes the following:

•The factors in the tumor microenvironment contribute to ovarian cancer progress;
•New drug development for recurrent ovarian cancer treatment;
•The early DNA methylation profiles contribute to cancer development in late life;
•The special changes in the tumor microenvironment;
•Epigenetics and epigenomics.
*The impact of lipid metabolism in the tumor microenvironment in cancer progression and treatment.
*Impact of ferroptosis in endometriosis development. 

Dr. Huang has received an R03 funding titled “Role of Age-Related Changes in the Tumor Microenvironment on Ovarian Cancer Progression” from NIA at NIH for 2021-2023.
Dr. Huang received Charles B. Hammond's Research Fund from the Department of Obstetrics and Gynecology at Duke University in November 2022, for a project titled "Single Cell Spatial Transcriptomics in Highly Aggressive and Less Aggressive Ovarian Cancer".
Dr. Huang has received Duke Cancer Institute 2023 spring pilot study award for07012023-06302024, the project title is "Age Effects on Chemotherapy Targeting Cells Causing Ovarian Cancer Recurrence”.
Dr. Huang has received the American Cancer Society -Duke Cancer Institute (ASC-DCI) 2024 spring pilot study award for 07012024-06302025. The project title is "Early Establishment of Epigenetic Profiles that Increase Cancer Risk in Late Life”.
Dr. Huang received Charles B. Hammond's Research Fund from the Department of Obstetrics and Gynecology at Duke University in November 2023 for 01012024-12312024. The project's title is "Age Effects on Chemotherapy Targeting Cells Causing Ovarian Cancer Recurrence".


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