Cargando…

Characterisation and localisation of the endocannabinoid system components in the adult human testis

Heavy use of cannabis (marijuana) has been associated with decreased semen quality, which may reflect disruption of the endocannabinoid system (ECS) in the male reproductive tract by exogenous cannabinoids. Components of ECS have been previously described in human spermatozoa and in the rodent testi...

Descripción completa

Detalles Bibliográficos
Autores principales: Nielsen, John E., Rolland, Antoine D., Rajpert-De Meyts, Ewa, Janfelt, Christian, Jørgensen, Anne, Winge, Sofia B., Kristensen, David M., Juul, Anders, Chalmel, Frédéric, Jégou, Bernard, Skakkebaek, Niels E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753062/
https://www.ncbi.nlm.nih.gov/pubmed/31537814
http://dx.doi.org/10.1038/s41598-019-49177-y
_version_ 1783452817654022144
author Nielsen, John E.
Rolland, Antoine D.
Rajpert-De Meyts, Ewa
Janfelt, Christian
Jørgensen, Anne
Winge, Sofia B.
Kristensen, David M.
Juul, Anders
Chalmel, Frédéric
Jégou, Bernard
Skakkebaek, Niels E.
author_facet Nielsen, John E.
Rolland, Antoine D.
Rajpert-De Meyts, Ewa
Janfelt, Christian
Jørgensen, Anne
Winge, Sofia B.
Kristensen, David M.
Juul, Anders
Chalmel, Frédéric
Jégou, Bernard
Skakkebaek, Niels E.
author_sort Nielsen, John E.
collection PubMed
description Heavy use of cannabis (marijuana) has been associated with decreased semen quality, which may reflect disruption of the endocannabinoid system (ECS) in the male reproductive tract by exogenous cannabinoids. Components of ECS have been previously described in human spermatozoa and in the rodent testis but there is little information on the ECS expression within the human testis. In this study we characterised the main components of the ECS by immunohistochemistry (IHC) on archived testis tissue samples from 15 patients, and by in silico analysis of existing transcriptome datasets from testicular cell populations. The presence of 2-arachidonoylglycerol (2-AG) in the human testis was confirmed by matrix-assisted laser desorption ionization imaging analysis. Endocannabinoid-synthesising enzymes; diacylglycerol lipase (DAGL) and N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), were detected in germ cells and somatic cells, respectively. The cannabinoid receptors, CNR1 and CNR2 were detected at a low level in post-meiotic germ cells and Leydig- and peritubular cells. Different transcripts encoding distinct receptor isoforms (CB1, CB1A, CB1B and CB2A) were also differentially distributed, mainly in germ cells. The cannabinoid-metabolising enzymes were abundantly present; the α/β-hydrolase domain-containing protein 2 (ABHD2) in all germ cell types, except early spermatocytes, the monoacylglycerol lipase (MGLL) in Sertoli cells, and the fatty acid amide hydrolase (FAAH) in late spermatocytes and post-meiotic germ cells. Our findings are consistent with a direct involvement of the ECS in regulation of human testicular physiology, including spermatogenesis and Leydig cell function. The study provides new evidence supporting observations that recreational cannabis can have possible deleterious effects on human testicular function.
format Online
Article
Text
id pubmed-6753062
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-67530622019-10-01 Characterisation and localisation of the endocannabinoid system components in the adult human testis Nielsen, John E. Rolland, Antoine D. Rajpert-De Meyts, Ewa Janfelt, Christian Jørgensen, Anne Winge, Sofia B. Kristensen, David M. Juul, Anders Chalmel, Frédéric Jégou, Bernard Skakkebaek, Niels E. Sci Rep Article Heavy use of cannabis (marijuana) has been associated with decreased semen quality, which may reflect disruption of the endocannabinoid system (ECS) in the male reproductive tract by exogenous cannabinoids. Components of ECS have been previously described in human spermatozoa and in the rodent testis but there is little information on the ECS expression within the human testis. In this study we characterised the main components of the ECS by immunohistochemistry (IHC) on archived testis tissue samples from 15 patients, and by in silico analysis of existing transcriptome datasets from testicular cell populations. The presence of 2-arachidonoylglycerol (2-AG) in the human testis was confirmed by matrix-assisted laser desorption ionization imaging analysis. Endocannabinoid-synthesising enzymes; diacylglycerol lipase (DAGL) and N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), were detected in germ cells and somatic cells, respectively. The cannabinoid receptors, CNR1 and CNR2 were detected at a low level in post-meiotic germ cells and Leydig- and peritubular cells. Different transcripts encoding distinct receptor isoforms (CB1, CB1A, CB1B and CB2A) were also differentially distributed, mainly in germ cells. The cannabinoid-metabolising enzymes were abundantly present; the α/β-hydrolase domain-containing protein 2 (ABHD2) in all germ cell types, except early spermatocytes, the monoacylglycerol lipase (MGLL) in Sertoli cells, and the fatty acid amide hydrolase (FAAH) in late spermatocytes and post-meiotic germ cells. Our findings are consistent with a direct involvement of the ECS in regulation of human testicular physiology, including spermatogenesis and Leydig cell function. The study provides new evidence supporting observations that recreational cannabis can have possible deleterious effects on human testicular function. Nature Publishing Group UK 2019-09-19 /pmc/articles/PMC6753062/ /pubmed/31537814 http://dx.doi.org/10.1038/s41598-019-49177-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Nielsen, John E.
Rolland, Antoine D.
Rajpert-De Meyts, Ewa
Janfelt, Christian
Jørgensen, Anne
Winge, Sofia B.
Kristensen, David M.
Juul, Anders
Chalmel, Frédéric
Jégou, Bernard
Skakkebaek, Niels E.
Characterisation and localisation of the endocannabinoid system components in the adult human testis
title Characterisation and localisation of the endocannabinoid system components in the adult human testis
title_full Characterisation and localisation of the endocannabinoid system components in the adult human testis
title_fullStr Characterisation and localisation of the endocannabinoid system components in the adult human testis
title_full_unstemmed Characterisation and localisation of the endocannabinoid system components in the adult human testis
title_short Characterisation and localisation of the endocannabinoid system components in the adult human testis
title_sort characterisation and localisation of the endocannabinoid system components in the adult human testis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753062/
https://www.ncbi.nlm.nih.gov/pubmed/31537814
http://dx.doi.org/10.1038/s41598-019-49177-y
work_keys_str_mv AT nielsenjohne characterisationandlocalisationoftheendocannabinoidsystemcomponentsintheadulthumantestis
AT rollandantoined characterisationandlocalisationoftheendocannabinoidsystemcomponentsintheadulthumantestis
AT rajpertdemeytsewa characterisationandlocalisationoftheendocannabinoidsystemcomponentsintheadulthumantestis
AT janfeltchristian characterisationandlocalisationoftheendocannabinoidsystemcomponentsintheadulthumantestis
AT jørgensenanne characterisationandlocalisationoftheendocannabinoidsystemcomponentsintheadulthumantestis
AT wingesofiab characterisationandlocalisationoftheendocannabinoidsystemcomponentsintheadulthumantestis
AT kristensendavidm characterisationandlocalisationoftheendocannabinoidsystemcomponentsintheadulthumantestis
AT juulanders characterisationandlocalisationoftheendocannabinoidsystemcomponentsintheadulthumantestis
AT chalmelfrederic characterisationandlocalisationoftheendocannabinoidsystemcomponentsintheadulthumantestis
AT jegoubernard characterisationandlocalisationoftheendocannabinoidsystemcomponentsintheadulthumantestis
AT skakkebaeknielse characterisationandlocalisationoftheendocannabinoidsystemcomponentsintheadulthumantestis