The reported adverse effects of marijuana use, its growing availability and consumption in recent years have heightened public concern. The national debate between those pressuring for its legalization and those supporting its ban will continue until the adverse and beneficial effects of this drug are clearly defined. One of the major concerns, among many central and peripheral effects of habitual marijuana smoking or exposure to cannabinoid derivatives, is their reported adverse effects on reproductive functions, including retard embryonic growth, pregnancy failure and poor fertilizing capacity of sperm. The mechanism(s) by which these cannabinoid effects are mediated are poorly defined. Recent identification and cloning of G-protein coupled cannabinoid receptors in the brain (CB1-R) and spleen (CB2-R) provide evidence that many of these effects are mediated via these receptors. Further, a putative endogenous cannabinoid ligand, arachidonoylethanolamide (anandamide) has been detected in the brain. Our recent finding of expression of cannabinoid receptors in the preimplantation mouse embryo and uterus, as well as anandamide synthesizing capacity in the uterus and oviduct also place these tissues as targets for cannabinoid ligand-receptor signaling and prompted us to continue investigation on this signaling pathway during early pregnancy.
Our specific aims are to determine in the mouse: (1) Expression and regulation of the CB1-R and CB2-R genes in the embryo and uterus during early pregnancy (days 1-8), (2) Anandamide synthesizing and (3) Anandamide hydrolyzing capacities, and their regulation in the oviduct and uterus during this period and under steroid hormonal stimulation, (4) Status of phospholipase A2 and phospholipase D activities in these tissues under these conditions, and (5) Roles of cannabinoid-ligand receptor signaling in the embryo and uterus during early pregnancy. We will use multiple experimental approaches including reverse transcription-polymerase chain reaction (RT-PCR),l Northern blot and in situ hybridization, immunostaining, Western blotting, autoradiographic and Scatchard analysis of ligand binding, enzyme assays, embryo culture and transfer, and others to accomplish our goal. Since there are similarities between mouse and human preimplantation and implantation physiology, results of this investigation will further our knowledge that should be valuable for defining marijuana's role in women's health issues.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
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Human Development Research Subcommittee (NIDA)
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University of Kansas
Schools of Medicine
Kansas City
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Leishman, Emma; Manchanda, Meera; Thelen, Rachel et al. (2018) Cannabidiol's Upregulation of N-acyl Ethanolamines in the Central Nervous System Requires N-acyl Phosphatidyl Ethanolamine-Specific Phospholipase D. Cannabis Cannabinoid Res 3:228-241
Sun, Xiaofei; Tavenier, Alexandra; Deng, Wenbo et al. (2018) Metformin attenuates susceptibility to inflammation-induced preterm birth in mice with higher endocannabinoid levels. Biol Reprod 98:208-217
Yuan, Jia; Deng, Wenbo; Cha, Jeeyeon et al. (2018) Tridimensional visualization reveals direct communication between the embryo and glands critical for implantation. Nat Commun 9:603
Leishman, Emma; Kunkler, Phillip E; Manchanda, Meera et al. (2017) Environmental Toxin Acrolein Alters Levels of Endogenous Lipids, Including TRP Agonists: A Potential Mechanism for Headache Driven by TRPA1 Activation. Neurobiol Pain 1:28-36
Ho, Jacqueline M; Bergeon Burns, Christine M; Rendon, Nikki M et al. (2017) Lipid signaling and fat storage in the dark-eyed junco. Gen Comp Endocrinol 247:166-173
Rowley, Shane; Sun, Xiaofei; Lima, Isabel V et al. (2017) Cannabinoid receptor 1/2 double-knockout mice develop epilepsy. Epilepsia 58:e162-e166
Yuan, Jia; Cha, Jeeyeon; Deng, Wenbo et al. (2016) Planar cell polarity signaling in the uterus directs appropriate positioning of the crypt for embryo implantation. Proc Natl Acad Sci U S A 113:E8079-E8088
Deng, Wenbo; Cha, Jeeyeon; Yuan, Jia et al. (2016) p53 coordinates decidual sestrin 2/AMPK/mTORC1 signaling to govern parturition timing. J Clin Invest 126:2941-54
Leishman, Emma; Cornett, Ben; Spork, Karl et al. (2016) Broad impact of deleting endogenous cannabinoid hydrolyzing enzymes and the CB1 cannabinoid receptor on the endogenous cannabinoid-related lipidome in eight regions of the mouse brain. Pharmacol Res 110:159-172
Sun, Xiaofei; Deng, Wenbo; Li, Yingju et al. (2016) Sustained Endocannabinoid Signaling Compromises Decidual Function and Promotes Inflammation-induced Preterm Birth. J Biol Chem 291:8231-40

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