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Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis.
Hum Reprod. 2014 Aug; 29(8):1730-8.HR

Abstract

STUDY QUESTION

Are the transmembrane mucins, MUC1, MUC4 and MUC16, differentially expressed in endometriosis compared with normal endometrium?

SUMMARY ANSWER

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).

WHAT IS KNOWN ALREADY

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.

STUDY DESIGN, SIZE, DURATION

This was a laboratory-based study of samples from 12 endometriosis patients as well as non-endometriosis control samples obtained from 31 patients.

PARTICIPANTS/MATERIALS, SETTING, METHODS

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.

MAIN RESULTS AND THE ROLE OF CHANCE

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.

LIMITATIONS, REASONS FOR CAUTION

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.

WIDER IMPLICATIONS OF THE FINDINGS

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.

STUDY FUNDING

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.

Authors+Show Affiliations

Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251, USA.Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251, USA.Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251, USA.Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.Department of Obstetrics and Gynecology, Greenville Health System, Greenville, SC 29650, USA.Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251, USA Department of Biochemistry and Molecular Biology, M.D. Anderson Cancer Center, Houston, TX 77030, USA dcarson@rice.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24939955

Citation

Dharmaraj, N, et al. "Expression of the Transmembrane Mucins, MUC1, MUC4 and MUC16, in Normal Endometrium and in Endometriosis." Human Reproduction (Oxford, England), vol. 29, no. 8, 2014, pp. 1730-8.
Dharmaraj N, Chapela PJ, Morgado M, et al. Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis. Hum Reprod. 2014;29(8):1730-8.
Dharmaraj, N., Chapela, P. J., Morgado, M., Hawkins, S. M., Lessey, B. A., Young, S. L., & Carson, D. D. (2014). Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis. Human Reproduction (Oxford, England), 29(8), 1730-8. https://doi.org/10.1093/humrep/deu146
Dharmaraj N, et al. Expression of the Transmembrane Mucins, MUC1, MUC4 and MUC16, in Normal Endometrium and in Endometriosis. Hum Reprod. 2014;29(8):1730-8. PubMed PMID: 24939955.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis. AU - Dharmaraj,N, AU - Chapela,P J, AU - Morgado,M, AU - Hawkins,S M, AU - Lessey,B A, AU - Young,S L, AU - Carson,D D, Y1 - 2014/06/17/ PY - 2014/6/19/entrez PY - 2014/6/19/pubmed PY - 2015/4/8/medline KW - cytokeratin-18 KW - endometriosis KW - endometrium KW - mucins SP - 1730 EP - 8 JF - Human reproduction (Oxford, England) JO - Hum. Reprod. VL - 29 IS - 8 N2 - STUDY QUESTION: Are the transmembrane mucins, MUC1, MUC4 and MUC16, differentially expressed in endometriosis compared with normal endometrium? SUMMARY ANSWER: 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). WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: This was a laboratory-based study of samples from 12 endometriosis patients as well as non-endometriosis control samples obtained from 31 patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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. LIMITATIONS, REASONS FOR CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING: 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. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/24939955/Expression_of_the_transmembrane_mucins_MUC1_MUC4_and_MUC16_in_normal_endometrium_and_in_endometriosis_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/deu146 DB - PRIME DP - Unbound Medicine ER -