Cannabinoid exposure and altered DNA methylation in rat and human sperm.
Abstract
Little is known about the reproductive effects of paternal cannabis exposure. We evaluated
associations between cannabis or tetrahydrocannabinol (THC) exposure and altered DNA
methylation in sperm from humans and rats, respectively. DNA methylation, measured
by reduced representation bisulfite sequencing, differed in the sperm of human users
from non-users by at least 10% at 3,979 CpG sites. Pathway analyses indicated Hippo
Signaling and Pathways in Cancer as enriched with altered genes (Bonferroni p < 0.02).
These same two pathways were also enriched with genes having altered methylation in
sperm from THC-exposed versus vehicle-exposed rats (p < 0.01). Data validity is supported
by significant correlations between THC exposure levels in humans and methylation
for 177 genes, and substantial overlap in THC target genes in rat sperm (this study)
and genes previously reported as having altered methylation in the brain of rat offspring
born to parents both exposed to THC during adolescence. In humans, cannabis use was
also associated with significantly lower sperm concentration. Findings point to possible
pre-conception paternal reproductive risks associated with cannabis use.
Type
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https://hdl.handle.net/10161/18357Published Version (Please cite this version)
10.1080/15592294.2018.1554521Publication Info
(2018). Cannabinoid exposure and altered DNA methylation in rat and human sperm. Epigenetics, 13(12). pp. 1208-1221. 10.1080/15592294.2018.1554521. Retrieved from https://hdl.handle.net/10161/18357.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.
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Kelly S Acharya
Assistant Professor of Obstetrics and Gynecology
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 tr
Scott Haden Kollins
Adjunct Professor in the Department of Psychiatry and Behavioral Sciences
Scott H. Kollins, PhD received his undergraduate degree in psychology from Duke and
his Master’s and Doctorate degrees in Clinical Psychology from Auburn University.
After completing his clinical internship at the University of Mississippi Medical
Center, where he served as Chief Intern, he joined the faculty of the Department of
Psychology at Western Michigan University for three years, before joining the Duke
faculty in 2000. Dr. Kollins has published more than 125 scientific pap
Edward Daniel Levin
Professor in Psychiatry and Behavioral Sciences
Dr. Levin is Chief of the Neurobehavioral Research Lab in the Psychiatry Department
of Duke University Medical Center. His primary academic appointment is as Professor
in the Department of Psychiatry and Behavioral Sciences. He also has secondary appointments
in the Department Pharmacology and Cancer Biology, the Department of Psychological
and Brain Sciences and the Nicholas School of the Environment at Duke. His primary
research effort is to understand basic neural interactions underlying cogn
Joseph E. Lucas
Associate Research Professor in the Social Science Research Institute
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
F Joseph McClernon
Professor in Psychiatry and Behavioral Sciences
Joseph McClernon, Ph.D., is a professor in the Department of Psychiatry and Behavioral
Sciences and founder/director of the Center for Addiction Science and Technology (CfAST).
In his four years with the Duke Clinical and Translational Science Institute (CTSI)
he has served as director of the Evaluation and Strategic Planning core, interim co-director
of the Team Science core, and director of the Integration and Strategic Partnerships
pillar. During his tenure with CTSI, his leadership has be
John T Mitchell
Associate Professor in Psychiatry and Behavioral Sciences
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 r
Thomas Michael Price
Professor Emeritus of Obstetrics and Gynecology
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 incre
Douglas Joe Raburn
Assistant Professor of Obstetrics and Gynecology
Testis: Macrophage-Leydig cell functional interaction Sertoli cell-germ cell functional
interaction Action and regulation of B cell translocation gene 1 in the seminiferous
epithelium General: Ovarian Tissue CryopreservationInfertility Mechanism of fertilization
Mechanism of embryo implantation
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