Male obesity impacts DNA methylation reprogramming in sperm.
Date
2021-01-25
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Abstract
Background
Male obesity has profound effects on morbidity and mortality, but relatively little is known about the impact of obesity on gametes and the potential for adverse effects of male obesity to be passed to the next generation. DNA methylation contributes to gene regulation and is erased and re-established during gametogenesis. Throughout post-pubertal spermatogenesis, there are continual needs to both maintain established methylation and complete DNA methylation programming, even during epididymal maturation. This dynamic epigenetic landscape may confer increased vulnerability to environmental influences, including the obesogenic environment, that could disrupt reprogramming fidelity. Here we conducted an exploratory analysis that showed that overweight/obesity (n = 20) is associated with differences in mature spermatozoa DNA methylation profiles relative to controls with normal BMI (n = 47).Results
We identified 3264 CpG sites in human sperm that are significantly associated with BMI (p < 0.05) using Infinium HumanMethylation450 BeadChips. These CpG sites were significantly overrepresented among genes involved in transcriptional regulation and misregulation in cancer, nervous system development, and stem cell pluripotency. Analysis of individual sperm using bisulfite sequencing of cloned alleles revealed that the methylation differences are present in a subset of sperm rather than being randomly distributed across all sperm.Conclusions
Male obesity is associated with altered sperm DNA methylation profiles that appear to affect reprogramming fidelity in a subset of sperm, suggestive of an influence on the spermatogonia. Further work is required to determine the potential heritability of these DNA methylation alterations. If heritable, these changes have the potential to impede normal development.Type
Department
Description
Provenance
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Keyhan, Sanaz, Emily Burke, Rose Schrott, Zhiqing Huang, Carole Grenier, Thomas Price, Doug Raburn, David L Corcoran, et al. (2021). Male obesity impacts DNA methylation reprogramming in sperm. Clinical epigenetics, 13(1). p. 17. 10.1186/s13148-020-00997-0 Retrieved from https://hdl.handle.net/10161/22564.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke
Zhiqing Huang
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".
Thomas Michael Price
Dr. Price is involved in both clinical and basic science research. The main focus of the basic science molecular endocrinology laboratory is the study of novel sex steroid receptors. Currently, the work focuses on a novel progesterone receptor that localizes to the mitochondrion. Studies including RNAi in cell models and creation of transgenic mice are ongoing to discover the function of this receptor. The overall hypothesis is that progesterone modulates mitochondrial activity to meet the increased cellular energy demands of pregnancy via this receptor.
Dr. Price also participates in clinical research endeavors. These projects are constantly changing and focus on many aspects of reproductive endocrinology including ovarian preservation during chemotherapy, treatments for menorrhagia, endometriosis, leiomyomata and infertility.
Douglas Joe Raburn
Dr. Raburn is the Director of the Assisted Reproductive Technology Laboratories at the Duke Fertility Center. As part of the multidisciplinary team within the Reproductive Endocrinology and Infertility division, he specializes in optimizing outcomes for patients who require assisted reproduction for current and future family building. His research focuses on gamete, embryo and reproductive tissue biology.
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.