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

N. Dharmaraj, P. J. Chapela, M. Morgado, S. M. Hawkins, B. A. Lessey, S. L. Young, D. D. Carson

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

study question: Are the transmembrane mucins, MUC1, MUC4 and MUC16, differentially expressed in endometriosis compared with normal endometrium? summaryanswer: 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 b-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 ofMUC1andMUC16mRNArevealed that these mucins do not vary significantly during the menstrual cycle nor are they altered inwomenwith endometriosis relative to the epithelial marker, KRT18.MUC4mRNAis 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 b-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.

Original languageEnglish (US)
Pages (from-to)1730-1738
Number of pages9
JournalHuman Reproduction
Volume29
Issue number8
DOIs
StatePublished - Aug 2014
Externally publishedYes

Keywords

  • Cytokeratin-18
  • Endometriosis
  • Endometrium
  • Mucins

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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    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, 29(8), 1730-1738. https://doi.org/10.1093/humrep/deu146