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Impact of tetrahydrocannabinol on the endocannabinoid 2-arachidonoylglycerol metabolism: ABHD6 and ABHD12 as novel players in human placenta.
Biochim Biophys Acta Mol Cell Biol Lipids. 2020 12; 1865(12):158807.BB

Abstract

Cannabis use has been increasing worldwide for recreational and medical purposes. Consumption by pregnant women is associated with disturbances in pregnancy outcome, such as low birth weight, prematurity and intrauterine growth retardation, though the underlying biochemical mechanisms are unknown. The endocannabinoid system is involved in several reproductive events and the disruption of its homeostasis by ∆9-tetrahydrocannabinol (THC), the main psychoactive cannabinoid, may lead to a negative gestational outcome. In human placenta, THC impairs the levels of the endocannabinoid anandamide (AEA). The other major endocannabinoid, 2-arachidonoylglycerol (2-AG) also plays an important role on proper placentation and pregnancy success. However, THC impact on 2-AG homeostasis has never been addressed. Hence, the effects of THC in 2-AG levels and metabolic enzymes expression were explored. Long-term treatment impairs the expression of the main 2-AG synthetic and degradative enzymes. Curiously, with the highest concentration, despite the maintenance of diacylglycerol lipase alpha (DAGLα) and the decrease in monoacylglycerol lipase (MAGL) expression, 2-AG levels remain constant. Given the endocannabinoid signalling local tight regulation, we hypothesize the involvement of other 2-AG degradative enzymes. Indeed, THC increases the expression of the hydrolyzing enzymes alpha beta hydrolase domain-6 (ABHD6) and -12 (ABHD12), that we firstly describe in human placental tissues. The results show that THC, depending on time of exposure, induces alterations in 2-AG metabolic enzymes expression in placental explants, highlighting the importance of 2-AG regulation and endocannabinoid signalling in placental development. Alterations in this homeostasis may explain the negative pregnancy outcome related to cannabis consumption.

Authors+Show Affiliations

UCIBIO, REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.UCIBIO, REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.LAQV, REQUIMTE, Departamento de Ciências Químicas, Laboratório de Bromatologia e Hidrologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.Departamento da Mulher e da Medicina Reprodutiva, Serviço de Obstetrícia, Centro Materno-Infantil do Norte-Centro Hospitalar do Porto, Porto, Portugal.Departamento da Mulher e da Medicina Reprodutiva, Serviço de Obstetrícia, Centro Materno-Infantil do Norte-Centro Hospitalar do Porto, Porto, Portugal.UCIBIO, REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.UCIBIO, REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. Electronic address: george@ff.up.pt.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32829065

Citation

Maia, João, et al. "Impact of Tetrahydrocannabinol On the Endocannabinoid 2-arachidonoylglycerol Metabolism: ABHD6 and ABHD12 as Novel Players in Human Placenta." Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids, vol. 1865, no. 12, 2020, p. 158807.
Maia J, Fonseca BM, Cunha SC, et al. Impact of tetrahydrocannabinol on the endocannabinoid 2-arachidonoylglycerol metabolism: ABHD6 and ABHD12 as novel players in human placenta. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865(12):158807.
Maia, J., Fonseca, B. M., Cunha, S. C., Braga, J., Gonçalves, D., Teixeira, N., & Correia-da-Silva, G. (2020). Impact of tetrahydrocannabinol on the endocannabinoid 2-arachidonoylglycerol metabolism: ABHD6 and ABHD12 as novel players in human placenta. Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids, 1865(12), 158807. https://doi.org/10.1016/j.bbalip.2020.158807
Maia J, et al. Impact of Tetrahydrocannabinol On the Endocannabinoid 2-arachidonoylglycerol Metabolism: ABHD6 and ABHD12 as Novel Players in Human Placenta. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865(12):158807. PubMed PMID: 32829065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of tetrahydrocannabinol on the endocannabinoid 2-arachidonoylglycerol metabolism: ABHD6 and ABHD12 as novel players in human placenta. AU - Maia,João, AU - Fonseca,Bruno M, AU - Cunha,Sara C, AU - Braga,Jorge, AU - Gonçalves,Daniela, AU - Teixeira,Natércia, AU - Correia-da-Silva,Georgina, Y1 - 2020/08/21/ PY - 2020/05/13/received PY - 2020/08/03/revised PY - 2020/08/17/accepted PY - 2020/8/24/pubmed PY - 2021/1/5/medline PY - 2020/8/24/entrez KW - 2-Arachidonoylglycerol KW - ABHD12 KW - ABHD6 KW - Endocannabinoid system KW - Placenta explant KW - ∆(9)-Tetrahydrocannabinol SP - 158807 EP - 158807 JF - Biochimica et biophysica acta. Molecular and cell biology of lipids JO - Biochim Biophys Acta Mol Cell Biol Lipids VL - 1865 IS - 12 N2 - Cannabis use has been increasing worldwide for recreational and medical purposes. Consumption by pregnant women is associated with disturbances in pregnancy outcome, such as low birth weight, prematurity and intrauterine growth retardation, though the underlying biochemical mechanisms are unknown. The endocannabinoid system is involved in several reproductive events and the disruption of its homeostasis by ∆9-tetrahydrocannabinol (THC), the main psychoactive cannabinoid, may lead to a negative gestational outcome. In human placenta, THC impairs the levels of the endocannabinoid anandamide (AEA). The other major endocannabinoid, 2-arachidonoylglycerol (2-AG) also plays an important role on proper placentation and pregnancy success. However, THC impact on 2-AG homeostasis has never been addressed. Hence, the effects of THC in 2-AG levels and metabolic enzymes expression were explored. Long-term treatment impairs the expression of the main 2-AG synthetic and degradative enzymes. Curiously, with the highest concentration, despite the maintenance of diacylglycerol lipase alpha (DAGLα) and the decrease in monoacylglycerol lipase (MAGL) expression, 2-AG levels remain constant. Given the endocannabinoid signalling local tight regulation, we hypothesize the involvement of other 2-AG degradative enzymes. Indeed, THC increases the expression of the hydrolyzing enzymes alpha beta hydrolase domain-6 (ABHD6) and -12 (ABHD12), that we firstly describe in human placental tissues. The results show that THC, depending on time of exposure, induces alterations in 2-AG metabolic enzymes expression in placental explants, highlighting the importance of 2-AG regulation and endocannabinoid signalling in placental development. Alterations in this homeostasis may explain the negative pregnancy outcome related to cannabis consumption. SN - 1879-2618 UR - https://www.unboundmedicine.com/medline/citation/32829065/Impact_of_tetrahydrocannabinol_on_the_endocannabinoid_2_arachidonoylglycerol_metabolism:_ABHD6_and_ABHD12_as_novel_players_in_human_placenta_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1388-1981(20)30199-2 DB - PRIME DP - Unbound Medicine ER -