CB1 expression is attenuated in Fallopian tube and decidua of women with ectopic pregnancy

Embryo retention in the Fallopian tube (FT) is thought to lead to ectopic pregnancy (EP), a considerable cause of morbidity. In mice, genetic/pharmacological silencing of cannabinoid receptor Cnr1, encoding CB1, causes retention of embryos in the oviduct. The role of the endocannabinoids in tubal im...

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Veröffentlicht in:PloS one 2008-12, Vol.3 (12), p.e3969-e3969
Hauptverfasser: Horne, Andrew W, Phillips, 3rd, John A, Kane, Nicole, Lourenco, Paula C, McDonald, Sarah E, Williams, Alistair R W, Simon, Carlos, Dey, Sudhansu K, Critchley, Hilary O D
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container_title PloS one
container_volume 3
creator Horne, Andrew W
Phillips, 3rd, John A
Kane, Nicole
Lourenco, Paula C
McDonald, Sarah E
Williams, Alistair R W
Simon, Carlos
Dey, Sudhansu K
Critchley, Hilary O D
description Embryo retention in the Fallopian tube (FT) is thought to lead to ectopic pregnancy (EP), a considerable cause of morbidity. In mice, genetic/pharmacological silencing of cannabinoid receptor Cnr1, encoding CB1, causes retention of embryos in the oviduct. The role of the endocannabinoids in tubal implantation in humans is not known. Timed FT biopsies (n = 18) were collected from women undergoing gynecological procedures for benign conditions. Endometrial biopsies and whole blood were collected from women undergoing surgery for EP (n = 11); management of miscarriage (n = 6), and termination of pregnancy (n = 8). Using RT-PCR and immunohistochemistry, CB1 mRNA and protein expression levels/patterns were examined in FT and endometrial biopsies. The distribution of two polymorphisms of CNR1 was examined by TaqMan analysis of genomic DNA from the whole blood samples. In normal FT, CB1 mRNA was higher in luteal compared to follicular-phase (p
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In mice, genetic/pharmacological silencing of cannabinoid receptor Cnr1, encoding CB1, causes retention of embryos in the oviduct. The role of the endocannabinoids in tubal implantation in humans is not known. Timed FT biopsies (n = 18) were collected from women undergoing gynecological procedures for benign conditions. Endometrial biopsies and whole blood were collected from women undergoing surgery for EP (n = 11); management of miscarriage (n = 6), and termination of pregnancy (n = 8). Using RT-PCR and immunohistochemistry, CB1 mRNA and protein expression levels/patterns were examined in FT and endometrial biopsies. The distribution of two polymorphisms of CNR1 was examined by TaqMan analysis of genomic DNA from the whole blood samples. In normal FT, CB1 mRNA was higher in luteal compared to follicular-phase (p&lt;0.05). CB1 protein was located in smooth muscle of the wall and of endothelial vessels, and luminal epithelium of FT. In FT from women with EP, CB1 mRNA expression was low. CB1 mRNA expression was also significantly lower (p&lt;0.05) in endometrium of women with EP compared to intrauterine pregnancies (IUP). Although of 1359G/A (rs1049353) polymorphisms of CNR1 gene suggests differential distribution of genotypes between the small, available cohorts of women with EP and those with IUP, results were not statistically significant. CB1 mRNA shows temporal variation in expression in human FT, likely regulated by progesterone. CB1 mRNA is expressed in low levels in both the FT and endometrium of women with EP. We propose that aberrant endocannabinoid-signaling in human FT leads to EP. Furthermore, our finding of reduced mRNA expression along with a possible association between polymorphism genotypes of the CNR1 gene and EP, suggests a possible genetic predisposition to EP that warrants replication in a larger sample pool.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0003969</identifier><identifier>PMID: 19093002</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Abortion ; Adolescent ; Adult ; Analysis ; Biology ; Biopsy ; Blood ; Blood vessels ; Brain research ; Cannabinoid CB1 receptors ; Cocaine ; Decidua ; Decidua - metabolism ; Decidua - pathology ; Deoxyribonucleic acid ; Differential distribution ; DNA ; Down-Regulation - genetics ; Ectopic pregnancy ; Embryonic development ; Embryos ; Endometrium ; Epithelium ; Fallopian tube ; Fallopian Tubes - metabolism ; Female ; Gene expression ; Gene polymorphism ; Genes ; Genetic polymorphisms ; Genetic Predisposition to Disease ; Genetics and Genomics ; Genotypes ; Growth factors ; Humans ; Immunohistochemistry ; Implantation ; Medical research ; Middle Aged ; Miscarriage ; Models, Biological ; Molecular Biology ; Morbidity ; Muscles ; Nicotine ; Oviduct ; Pharmacology ; Polymerase chain reaction ; Polymorphism ; Pregnancy ; Pregnancy complications ; Pregnancy, Ectopic - genetics ; Pregnancy, Ectopic - metabolism ; Pregnancy, Ectopic - pathology ; Pregnant women ; Progesterone ; Proteins ; Receptor, Cannabinoid, CB1 - genetics ; Receptor, Cannabinoid, CB1 - metabolism ; Retention ; RNA ; RNA, Messenger - metabolism ; Signaling ; Smooth muscle ; Statistical analysis ; Statistical methods ; Surgery ; Temporal variations ; Women's Health ; Young Adult</subject><ispartof>PloS one, 2008-12, Vol.3 (12), p.e3969-e3969</ispartof><rights>COPYRIGHT 2008 Public Library of Science</rights><rights>2008 Horne et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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In mice, genetic/pharmacological silencing of cannabinoid receptor Cnr1, encoding CB1, causes retention of embryos in the oviduct. The role of the endocannabinoids in tubal implantation in humans is not known. Timed FT biopsies (n = 18) were collected from women undergoing gynecological procedures for benign conditions. Endometrial biopsies and whole blood were collected from women undergoing surgery for EP (n = 11); management of miscarriage (n = 6), and termination of pregnancy (n = 8). Using RT-PCR and immunohistochemistry, CB1 mRNA and protein expression levels/patterns were examined in FT and endometrial biopsies. The distribution of two polymorphisms of CNR1 was examined by TaqMan analysis of genomic DNA from the whole blood samples. In normal FT, CB1 mRNA was higher in luteal compared to follicular-phase (p&lt;0.05). CB1 protein was located in smooth muscle of the wall and of endothelial vessels, and luminal epithelium of FT. In FT from women with EP, CB1 mRNA expression was low. CB1 mRNA expression was also significantly lower (p&lt;0.05) in endometrium of women with EP compared to intrauterine pregnancies (IUP). Although of 1359G/A (rs1049353) polymorphisms of CNR1 gene suggests differential distribution of genotypes between the small, available cohorts of women with EP and those with IUP, results were not statistically significant. CB1 mRNA shows temporal variation in expression in human FT, likely regulated by progesterone. CB1 mRNA is expressed in low levels in both the FT and endometrium of women with EP. We propose that aberrant endocannabinoid-signaling in human FT leads to EP. Furthermore, our finding of reduced mRNA expression along with a possible association between polymorphism genotypes of the CNR1 gene and EP, suggests a possible genetic predisposition to EP that warrants replication in a larger sample pool.</description><subject>Aberration</subject><subject>Abortion</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Analysis</subject><subject>Biology</subject><subject>Biopsy</subject><subject>Blood</subject><subject>Blood vessels</subject><subject>Brain research</subject><subject>Cannabinoid CB1 receptors</subject><subject>Cocaine</subject><subject>Decidua</subject><subject>Decidua - metabolism</subject><subject>Decidua - pathology</subject><subject>Deoxyribonucleic acid</subject><subject>Differential distribution</subject><subject>DNA</subject><subject>Down-Regulation - genetics</subject><subject>Ectopic pregnancy</subject><subject>Embryonic development</subject><subject>Embryos</subject><subject>Endometrium</subject><subject>Epithelium</subject><subject>Fallopian tube</subject><subject>Fallopian Tubes - metabolism</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene polymorphism</subject><subject>Genes</subject><subject>Genetic polymorphisms</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics and Genomics</subject><subject>Genotypes</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Implantation</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>Miscarriage</subject><subject>Models, Biological</subject><subject>Molecular Biology</subject><subject>Morbidity</subject><subject>Muscles</subject><subject>Nicotine</subject><subject>Oviduct</subject><subject>Pharmacology</subject><subject>Polymerase chain reaction</subject><subject>Polymorphism</subject><subject>Pregnancy</subject><subject>Pregnancy complications</subject><subject>Pregnancy, Ectopic - genetics</subject><subject>Pregnancy, Ectopic - metabolism</subject><subject>Pregnancy, Ectopic - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Horne, Andrew W</au><au>Phillips, 3rd, John A</au><au>Kane, Nicole</au><au>Lourenco, Paula C</au><au>McDonald, Sarah E</au><au>Williams, Alistair R W</au><au>Simon, Carlos</au><au>Dey, Sudhansu K</au><au>Critchley, Hilary O D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CB1 expression is attenuated in Fallopian tube and decidua of women with ectopic pregnancy</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2008-12-18</date><risdate>2008</risdate><volume>3</volume><issue>12</issue><spage>e3969</spage><epage>e3969</epage><pages>e3969-e3969</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Embryo retention in the Fallopian tube (FT) is thought to lead to ectopic pregnancy (EP), a considerable cause of morbidity. In mice, genetic/pharmacological silencing of cannabinoid receptor Cnr1, encoding CB1, causes retention of embryos in the oviduct. The role of the endocannabinoids in tubal implantation in humans is not known. Timed FT biopsies (n = 18) were collected from women undergoing gynecological procedures for benign conditions. Endometrial biopsies and whole blood were collected from women undergoing surgery for EP (n = 11); management of miscarriage (n = 6), and termination of pregnancy (n = 8). Using RT-PCR and immunohistochemistry, CB1 mRNA and protein expression levels/patterns were examined in FT and endometrial biopsies. The distribution of two polymorphisms of CNR1 was examined by TaqMan analysis of genomic DNA from the whole blood samples. In normal FT, CB1 mRNA was higher in luteal compared to follicular-phase (p&lt;0.05). CB1 protein was located in smooth muscle of the wall and of endothelial vessels, and luminal epithelium of FT. In FT from women with EP, CB1 mRNA expression was low. CB1 mRNA expression was also significantly lower (p&lt;0.05) in endometrium of women with EP compared to intrauterine pregnancies (IUP). Although of 1359G/A (rs1049353) polymorphisms of CNR1 gene suggests differential distribution of genotypes between the small, available cohorts of women with EP and those with IUP, results were not statistically significant. CB1 mRNA shows temporal variation in expression in human FT, likely regulated by progesterone. CB1 mRNA is expressed in low levels in both the FT and endometrium of women with EP. We propose that aberrant endocannabinoid-signaling in human FT leads to EP. Furthermore, our finding of reduced mRNA expression along with a possible association between polymorphism genotypes of the CNR1 gene and EP, suggests a possible genetic predisposition to EP that warrants replication in a larger sample pool.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19093002</pmid><doi>10.1371/journal.pone.0003969</doi><tpages>e3969</tpages><oa>free_for_read</oa></addata></record>
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ispartof PloS one, 2008-12, Vol.3 (12), p.e3969-e3969
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1932-6203
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subjects Aberration
Abortion
Adolescent
Adult
Analysis
Biology
Biopsy
Blood
Blood vessels
Brain research
Cannabinoid CB1 receptors
Cocaine
Decidua
Decidua - metabolism
Decidua - pathology
Deoxyribonucleic acid
Differential distribution
DNA
Down-Regulation - genetics
Ectopic pregnancy
Embryonic development
Embryos
Endometrium
Epithelium
Fallopian tube
Fallopian Tubes - metabolism
Female
Gene expression
Gene polymorphism
Genes
Genetic polymorphisms
Genetic Predisposition to Disease
Genetics and Genomics
Genotypes
Growth factors
Humans
Immunohistochemistry
Implantation
Medical research
Middle Aged
Miscarriage
Models, Biological
Molecular Biology
Morbidity
Muscles
Nicotine
Oviduct
Pharmacology
Polymerase chain reaction
Polymorphism
Pregnancy
Pregnancy complications
Pregnancy, Ectopic - genetics
Pregnancy, Ectopic - metabolism
Pregnancy, Ectopic - pathology
Pregnant women
Progesterone
Proteins
Receptor, Cannabinoid, CB1 - genetics
Receptor, Cannabinoid, CB1 - metabolism
Retention
RNA
RNA, Messenger - metabolism
Signaling
Smooth muscle
Statistical analysis
Statistical methods
Surgery
Temporal variations
Women's Health
Young Adult
title CB1 expression is attenuated in Fallopian tube and decidua of women with ectopic pregnancy
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