Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis

Are the transmembrane mucins, MUC1, MUC4 and MUC16, differentially expressed in endometriosis compared with normal endometrium? This study revealed that transmembrane mucin expression does not vary significantly in normal endometrium during the menstrual cycle and is not altered in endometriosis rel...

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Veröffentlicht in:Human reproduction (Oxford) 2014-08, Vol.29 (8), p.1730-1738
Hauptverfasser: Dharmaraj, N, Chapela, P J, Morgado, M, Hawkins, S M, Lessey, B A, Young, S L, Carson, D D
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container_end_page 1738
container_issue 8
container_start_page 1730
container_title Human reproduction (Oxford)
container_volume 29
creator Dharmaraj, N
Chapela, P J
Morgado, M
Hawkins, S M
Lessey, B A
Young, S L
Carson, D D
description Are the transmembrane mucins, MUC1, MUC4 and MUC16, differentially expressed in endometriosis compared with normal endometrium? This study revealed that transmembrane mucin expression does not vary significantly in normal endometrium during the menstrual cycle and is not altered in endometriosis relative to the epithelial marker, cytokeratin-18 (KRT18). Increased serum levels of the transmembrane mucin fragments MUC1, MUC4 and MUC16 that normally dominate the apical surface of simple epithelia are found in several pathological conditions, including endometriosis. Altered mucin expression in gynecologic diseases may promote infertility or endometrial pathologies. This was a laboratory-based study of samples from 12 endometriosis patients as well as non-endometriosis control samples obtained from 31 patients. Total RNA was isolated from endometrial biopsies of ectopic and eutopic endometrium from women with endometriosis and control patients from different stages of the menstrual cycle. Quantitative (q)-RT-PCR analyses were performed for the mucins, MUC1, MUC4 and MUC16, relative to the epithelial marker, cytokeratin-18 (KRT18), or β-actin (ACTB). Frozen sections from endometrial biopsies of proliferative and mid-secretory stage women with endometriosis were immunostained for MUC1, MUC4 and MUC16. qRT-PCR analyses of MUC1 and MUC16 mRNA revealed that these mucins do not vary significantly during the menstrual cycle nor are they altered in women with endometriosis relative to the epithelial marker, KRT18. MUC4 mRNA is expressed at very low levels relative to MUC1 and MUC16 under all conditions. There was little difference in MUC1 and MUC16 expression between eutopic endometrial and ectopic endometriotic tissues. MUC4 expression also was not significantly higher in the ectopic endometriotic tissues. Immunostaining for all three mucins reveals robust expression of MUC1 and MUC16 at the apical surfaces of endometrial epithelia, but little to no staining for MUC4. qRT-PCR analysis was the main method used for mucin detection. Additional studies with stage III-IV endometriotic tissue would be useful to determine if changes in MUC1 and MUC16 expression occur, or if MUC4 expression increases, at later stages of endometriosis. We report a comprehensive comparative profile of the major transmembrane mucins, MUC1, MUC4 and MUC16, relative to the epithelial marker, KRT18, in normal cycling endometrium and in endometriosis, and indicate constitutive expression. Previous
doi_str_mv 10.1093/humrep/deu146
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This study revealed that transmembrane mucin expression does not vary significantly in normal endometrium during the menstrual cycle and is not altered in endometriosis relative to the epithelial marker, cytokeratin-18 (KRT18). Increased serum levels of the transmembrane mucin fragments MUC1, MUC4 and MUC16 that normally dominate the apical surface of simple epithelia are found in several pathological conditions, including endometriosis. Altered mucin expression in gynecologic diseases may promote infertility or endometrial pathologies. This was a laboratory-based study of samples from 12 endometriosis patients as well as non-endometriosis control samples obtained from 31 patients. Total RNA was isolated from endometrial biopsies of ectopic and eutopic endometrium from women with endometriosis and control patients from different stages of the menstrual cycle. Quantitative (q)-RT-PCR analyses were performed for the mucins, MUC1, MUC4 and MUC16, relative to the epithelial marker, cytokeratin-18 (KRT18), or β-actin (ACTB). Frozen sections from endometrial biopsies of proliferative and mid-secretory stage women with endometriosis were immunostained for MUC1, MUC4 and MUC16. qRT-PCR analyses of MUC1 and MUC16 mRNA revealed that these mucins do not vary significantly during the menstrual cycle nor are they altered in women with endometriosis relative to the epithelial marker, KRT18. MUC4 mRNA is expressed at very low levels relative to MUC1 and MUC16 under all conditions. There was little difference in MUC1 and MUC16 expression between eutopic endometrial and ectopic endometriotic tissues. MUC4 expression also was not significantly higher in the ectopic endometriotic tissues. Immunostaining for all three mucins reveals robust expression of MUC1 and MUC16 at the apical surfaces of endometrial epithelia, but little to no staining for MUC4. qRT-PCR analysis was the main method used for mucin detection. Additional studies with stage III-IV endometriotic tissue would be useful to determine if changes in MUC1 and MUC16 expression occur, or if MUC4 expression increases, at later stages of endometriosis. We report a comprehensive comparative profile of the major transmembrane mucins, MUC1, MUC4 and MUC16, relative to the epithelial marker, KRT18, in normal cycling endometrium and in endometriosis, and indicate constitutive expression. Previous studies have profiled the expression of individual mucins relative to β-actin and indicate accumulation in the luteal phase. Thus, these differences in interpretation appear to reflect the increased epithelial content of endometrium during the luteal phase. This study was supported by: NIH R01HD29963 to D.D.C.; NIH U54HD007495 to S.M.H.; and NIH R01HD067721 to S.L.Y. and B.A.L. The authors have no competing interests to declare.</description><identifier>ISSN: 0268-1161</identifier><identifier>EISSN: 1460-2350</identifier><identifier>DOI: 10.1093/humrep/deu146</identifier><identifier>PMID: 24939955</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>CA-125 Antigen - metabolism ; Endometriosis - metabolism ; Endometrium - metabolism ; Female ; Gene Expression ; Humans ; Membrane Proteins - metabolism ; Menstrual Cycle - metabolism ; Mucin-1 - metabolism ; Mucin-4 - metabolism ; Original</subject><ispartof>Human reproduction (Oxford), 2014-08, Vol.29 (8), p.1730-1738</ispartof><rights>The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. 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This study revealed that transmembrane mucin expression does not vary significantly in normal endometrium during the menstrual cycle and is not altered in endometriosis relative to the epithelial marker, cytokeratin-18 (KRT18). Increased serum levels of the transmembrane mucin fragments MUC1, MUC4 and MUC16 that normally dominate the apical surface of simple epithelia are found in several pathological conditions, including endometriosis. Altered mucin expression in gynecologic diseases may promote infertility or endometrial pathologies. This was a laboratory-based study of samples from 12 endometriosis patients as well as non-endometriosis control samples obtained from 31 patients. Total RNA was isolated from endometrial biopsies of ectopic and eutopic endometrium from women with endometriosis and control patients from different stages of the menstrual cycle. Quantitative (q)-RT-PCR analyses were performed for the mucins, MUC1, MUC4 and MUC16, relative to the epithelial marker, cytokeratin-18 (KRT18), or β-actin (ACTB). Frozen sections from endometrial biopsies of proliferative and mid-secretory stage women with endometriosis were immunostained for MUC1, MUC4 and MUC16. qRT-PCR analyses of MUC1 and MUC16 mRNA revealed that these mucins do not vary significantly during the menstrual cycle nor are they altered in women with endometriosis relative to the epithelial marker, KRT18. MUC4 mRNA is expressed at very low levels relative to MUC1 and MUC16 under all conditions. There was little difference in MUC1 and MUC16 expression between eutopic endometrial and ectopic endometriotic tissues. MUC4 expression also was not significantly higher in the ectopic endometriotic tissues. Immunostaining for all three mucins reveals robust expression of MUC1 and MUC16 at the apical surfaces of endometrial epithelia, but little to no staining for MUC4. qRT-PCR analysis was the main method used for mucin detection. Additional studies with stage III-IV endometriotic tissue would be useful to determine if changes in MUC1 and MUC16 expression occur, or if MUC4 expression increases, at later stages of endometriosis. We report a comprehensive comparative profile of the major transmembrane mucins, MUC1, MUC4 and MUC16, relative to the epithelial marker, KRT18, in normal cycling endometrium and in endometriosis, and indicate constitutive expression. Previous studies have profiled the expression of individual mucins relative to β-actin and indicate accumulation in the luteal phase. Thus, these differences in interpretation appear to reflect the increased epithelial content of endometrium during the luteal phase. This study was supported by: NIH R01HD29963 to D.D.C.; NIH U54HD007495 to S.M.H.; and NIH R01HD067721 to S.L.Y. and B.A.L. The authors have no competing interests to declare.</description><subject>CA-125 Antigen - metabolism</subject><subject>Endometriosis - metabolism</subject><subject>Endometrium - metabolism</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Humans</subject><subject>Membrane Proteins - metabolism</subject><subject>Menstrual Cycle - metabolism</subject><subject>Mucin-1 - metabolism</subject><subject>Mucin-4 - metabolism</subject><subject>Original</subject><issn>0268-1161</issn><issn>1460-2350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1P4zAQhi3ECkqXI1fkIwdCPfFXfEFCFV8Sq70sZ8tJHGoU28VOEPvvN22hYi8ztufR65l5EToDcgVE0cVq9MmuF60dgYkDNJsiKUrKySGakVJUBYCAY3SS8ysh07ESR-i4ZIoqxfkMrW4_1snm7GLAscPDyuIhmZC99fWULfZj40K-xL-el7CNDJvQbq_iEruAQ0ze9NiGNno7JDf6LTBV9k8xu_wT_ehMn-3pZ56j57vbP8uH4un3_ePy5qloaCWHopayg7q1AKblDfCSCiCiNpwJ0XJQUjFgquqgBMpLw6iSsq2kqUDZugNB5-h6p7sea2_bxoZpnl6vk_Mm_dXROP1_JbiVfonvmpHNTjYCF58CKb6NNg_au9zYvp-2EcesgTMmWSkln9BihzYp5pxst_8GiN64o3fu6J07E3_-vbc9_WUH_QcQiY0T</recordid><startdate>20140801</startdate><enddate>20140801</enddate><creator>Dharmaraj, N</creator><creator>Chapela, P J</creator><creator>Morgado, M</creator><creator>Hawkins, S M</creator><creator>Lessey, B A</creator><creator>Young, S L</creator><creator>Carson, D D</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140801</creationdate><title>Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis</title><author>Dharmaraj, N ; Chapela, P J ; Morgado, M ; Hawkins, S M ; Lessey, B A ; Young, S L ; Carson, D D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-b77f1bde11ad5c15236106ba5466d5197941498f121352a43977d87a819ebf163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>CA-125 Antigen - metabolism</topic><topic>Endometriosis - metabolism</topic><topic>Endometrium - metabolism</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Humans</topic><topic>Membrane Proteins - metabolism</topic><topic>Menstrual Cycle - metabolism</topic><topic>Mucin-1 - metabolism</topic><topic>Mucin-4 - metabolism</topic><topic>Original</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dharmaraj, N</creatorcontrib><creatorcontrib>Chapela, P J</creatorcontrib><creatorcontrib>Morgado, M</creatorcontrib><creatorcontrib>Hawkins, S M</creatorcontrib><creatorcontrib>Lessey, B A</creatorcontrib><creatorcontrib>Young, S L</creatorcontrib><creatorcontrib>Carson, D D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human reproduction (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dharmaraj, N</au><au>Chapela, P J</au><au>Morgado, M</au><au>Hawkins, S M</au><au>Lessey, B A</au><au>Young, S L</au><au>Carson, D D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis</atitle><jtitle>Human reproduction (Oxford)</jtitle><addtitle>Hum Reprod</addtitle><date>2014-08-01</date><risdate>2014</risdate><volume>29</volume><issue>8</issue><spage>1730</spage><epage>1738</epage><pages>1730-1738</pages><issn>0268-1161</issn><eissn>1460-2350</eissn><abstract>Are the transmembrane mucins, MUC1, MUC4 and MUC16, differentially expressed in endometriosis compared with normal endometrium? This study revealed that transmembrane mucin expression does not vary significantly in normal endometrium during the menstrual cycle and is not altered in endometriosis relative to the epithelial marker, cytokeratin-18 (KRT18). Increased serum levels of the transmembrane mucin fragments MUC1, MUC4 and MUC16 that normally dominate the apical surface of simple epithelia are found in several pathological conditions, including endometriosis. Altered mucin expression in gynecologic diseases may promote infertility or endometrial pathologies. This was a laboratory-based study of samples from 12 endometriosis patients as well as non-endometriosis control samples obtained from 31 patients. Total RNA was isolated from endometrial biopsies of ectopic and eutopic endometrium from women with endometriosis and control patients from different stages of the menstrual cycle. Quantitative (q)-RT-PCR analyses were performed for the mucins, MUC1, MUC4 and MUC16, relative to the epithelial marker, cytokeratin-18 (KRT18), or β-actin (ACTB). Frozen sections from endometrial biopsies of proliferative and mid-secretory stage women with endometriosis were immunostained for MUC1, MUC4 and MUC16. qRT-PCR analyses of MUC1 and MUC16 mRNA revealed that these mucins do not vary significantly during the menstrual cycle nor are they altered in women with endometriosis relative to the epithelial marker, KRT18. MUC4 mRNA is expressed at very low levels relative to MUC1 and MUC16 under all conditions. There was little difference in MUC1 and MUC16 expression between eutopic endometrial and ectopic endometriotic tissues. MUC4 expression also was not significantly higher in the ectopic endometriotic tissues. Immunostaining for all three mucins reveals robust expression of MUC1 and MUC16 at the apical surfaces of endometrial epithelia, but little to no staining for MUC4. qRT-PCR analysis was the main method used for mucin detection. Additional studies with stage III-IV endometriotic tissue would be useful to determine if changes in MUC1 and MUC16 expression occur, or if MUC4 expression increases, at later stages of endometriosis. We report a comprehensive comparative profile of the major transmembrane mucins, MUC1, MUC4 and MUC16, relative to the epithelial marker, KRT18, in normal cycling endometrium and in endometriosis, and indicate constitutive expression. Previous studies have profiled the expression of individual mucins relative to β-actin and indicate accumulation in the luteal phase. Thus, these differences in interpretation appear to reflect the increased epithelial content of endometrium during the luteal phase. This study was supported by: NIH R01HD29963 to D.D.C.; NIH U54HD007495 to S.M.H.; and NIH R01HD067721 to S.L.Y. and B.A.L. The authors have no competing interests to declare.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>24939955</pmid><doi>10.1093/humrep/deu146</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects CA-125 Antigen - metabolism
Endometriosis - metabolism
Endometrium - metabolism
Female
Gene Expression
Humans
Membrane Proteins - metabolism
Menstrual Cycle - metabolism
Mucin-1 - metabolism
Mucin-4 - metabolism
Original
title Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis
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