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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1080/15592294.2018.1554521

Publication Info

Murphy, Susan K, Nilda Itchon-Ramos, Zachary Visco, Zhiqing Huang, Carole Grenier, Rose Schrott, Kelly Acharya, Marie-Helene Boudreau, et al. (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.

Scholars@Duke

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. 

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”.

Acharya

Kelly S Acharya

Assistant Professor of Obstetrics and Gynecology
Price

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 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.

Raburn

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 Cryopreservation
Infertility
Mechanism of fertilization
Mechanism of embryo implantation

Mitchell

John T Mitchell

Associate Professor in Psychiatry and Behavioral Sciences
McClernon

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 been critical to building a culture of evaluation and continuous improvement, in strengthening the institute’s partnership with North Carolina Central University and other regional partners, and in planning strategy and development for the institute. 

 Dr. McClernon earned a Ph.D. in clinical psychology in 2001 from Southern Illinois University-Carbondale and completed a postdoctoral fellowship at Duke in 2002. He served as Director of the Addiction Division in Psychiatry and Behavioral Sciences from 2012-2020. His research is focused on increasing our understanding of tobacco use, developing new and more effective interventions to nicotine dependence, and informing the FDA’s regulation of tobacco products. He has served as a site-PI and Co-I for more than ten years in the Center for the Evaluation of Nicotine in Cigarettes (CENIC)— a national consortium that has provided the bulk of evidence to the FDA for informing national policies that will reduce nicotine in cigarettes to non-addictive levels, thus saving millions of lives. Dr. McClernon is now leading efforts to transition CENIC’s focus to public health interventions that ensure the new policy will be implemented in ways that enable equitable outcomes for marginalized groups. Other regulatory science research has evaluated the effects of nicotine in cigarettes on a model of cigarette experimentation, the impact of flavors in cigarettes and e-cigarettes, and the influence of product characteristics and policy on multiple tobacco product use. He has led other groundbreaking research on the influence of drug-associated environments on drug use, relapse, and treatment; tobacco use disparities among individuals with comorbid psychiatric (e.g., ADHD, serious mental illness) and health (e.g., HIV; chronic pain) problems.

Dr. McClernon has actively mentored early career individuals from high school students through early career faculty. His former postdoctoral fellows are faculty or staff scientists at academic medical centers, government agencies, and research institutes. He has been continuously NIH-, FDA-, and foundation- funded since 2002. He has authored/co-authored more than 170 peer-reviewed publications, has two patents, has served as chair of NIH grant review panels, and is the recipient of numerous awards including the Society for Research on Nicotine and Tobacco Jarvik-Russell New Investigator Award.

Levin

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 cognitive function and addiction and to apply this knowledge to better understand cognitive dysfunction and addiction disorders and to develop novel therapeutic treatments.

The three main research components of his laboratory are focused on the themes of the basic neurobiology of cognition and addiction, neurobehavioral toxicology and the development of novel therapeutic treatments for cognitive dysfunction and substance abuse. Currently, our principal research focus concerns nicotine. We have documented the basic effects of nicotine on learning memory and attention as well as nicotine self-administration. We are continuing with more mechanistic studies in rat models using selective lesions, local infusions and neurotransmitter interaction studies. We have found that nicotine improves memory performance not only in normal rats, but also in rats with lesions of hippocampal and basal forebrain connections. We are concentrating on alpha7 and alpha4beta2 nicotinic receptor subtypes in the hippocampus, amygdala , thalamus and frontal cortex and how they interact with dopamine D1 and D2 and glutamate NMDA systems with regard to memory and addiction. I am also conducting studies on human cognitive behavior. We have current studies to assess nicotine effects on attention, memory and mental processing speed in schizophrenia, Alzheimer's Disease and Attention Deficit Hyperactivity Disorder. In the area of neurobehavioral toxicology, I have continuing projects to characterize the adverse effects of prenatal and adolescent nicotine exposure. Our primary project in neurobehavioral toxicology focuses on the cognitive deficits caused by the marine toxins. The basic and applied aims of our research complement each other nicely. The findings concerning neural mechanisms underlying cognitive function help direct the behavioral toxicology and therapeutic development studies, while the applied studies provide important functional information concerning the importance of the basic mechanisms under investigation.

Kollins

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 papers in peer-reviewed journals.  Over the past 10 years, his research has been supported by 6 different federal agencies, including NICHD, NIDA, NIMH, NIEHS, NINDS, and EPA, and he currently holds a mid-career K24 award from NIDA.  He has also served as PI on more than 40 industry-funded clinical trials and is a consultant to a number of pharmaceutical companies in the area of ADHD clinical psychopharmacology.  He has served as a standing member of the Child Psychopathology and Developmental Disabilities study section and also served as an ad-hoc reviewer for 10 additional NIH study sections and 7 international granting agencies. He is an Associate Editor for the Journal of Attention Disorders and has reviewed for more than 50 different peer-reviewed journals. He is an elected member of the College on Problems of Drug Dependence and the American College of Neuropsychopharmacology. Dr. Kollins is a licensed clinical psychologist and maintains a practice through the ADHD Program’s outpatient clinic. His research interests are in the areas of psychopharmacology and the intersection of ADHD and substance abuse, particularly cigarette smoking.


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