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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Zhiqing Huang
Assistant Professor - Tracck V 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 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 modific
Scott Haden Kollins
Professor in 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
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 & Behavioral Sciences
Joe McClernon, Ph.D. is Professor and Director of the Addiction Division in the Department
of Psychiatry and Behavioral Sciences and is Founder/Director of the Center for Addiction
Science and Technology (CfAST) at the Duke University Medical Center. He earned a
Ph.D. in clinical psychology in 2001 from Southern Illinois University-Carbondale
and completed a postdoctoral fellowship at Duke in 2002. Joe’s research is focused
on increasing our understanding of tobacco and other addictions
John T Mitchell
Assistant Professor in Psychiatry and Behavioral Sciences
Susan Kay Murphy
Associate Professor in Obstetrics and Gynecology
Ovarian and cervical cancer epigenetics, imprinted genes in ovarian and cervical cancers,
identification of methylation biomarkers of disease, ovarian cancer stem cells, chemotherapeutic
response in ovarian cancer, tumor dormancy, the influence of the in utero environment
on DNA methylation and risk of disease.
Thomas Michael Price
Professor 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 in 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: Infertility Mechanism of fertilization Mechanism of embryo implantation
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