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      MSX1-expression during the different phases in healthy human endometrium

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          Abstract

          Purpose

          The human endometrium consists of different layers (basalis and functionalis) and undergoes different phases throughout the menstrual cycle. In a former paper, our research group was able to describe MSX1 as a positive prognosticator in endometrial carcinomas. The aim of this study was to examine the MSX1 expression in healthy endometrial tissue throughout the different phases to gain more insight on the mechanics of MSX-regulation in the female reproductive system.

          Materials and methods

          In this retrospective study, we investigated a total of 17 normal endometrial tissues (six during proliferative phase and five during early and six during late secretory phase). We used immunohistochemical staining and an immunoreactive score (IRS) to evaluate MSX1 expression. We also investigated correlations with other proteins, that have already been examined in our research group using the same patient collective.

          Results

          MSX1 is expressed in glandular cells during the proliferative phase and downregulated at early and late secretory phase ( p = 0.011). Also, a positive correlation between MSX1 and the progesterone-receptor A (PR-A) (correlation coefficient (cc) = 0.0671; p = 0.024), and the progesterone receptor B (PR-B) (cc = 0.0691; p = 0.018) was found. A trend towards negative correlation was recognized between MSX1 and Inhibin Beta-C-expression in glandular cells (cc = − 0.583; p-value = 0.060).

          Conclusion

          MSX1 is known as a member of the muscle segment homeobox gene family. MSX1 is a p53-interacting protein and overexpression of homeobox MSX1 induced apoptosis of cancer cells. Here we show that MSX1 is expressed especially in the proliferative phase of glandular epithelial tissue of the normal endometrium. The found positive correlation between MSX1 and progesterone receptors A and B confirms the results of a previous study on cancer tissue by our research group. Because MSX1 is known to be downregulated by progesterone, the found correlation of MSX1 and both PR-A and -B may represent a direct regulation of the MSX1 gene by a PR-response element. Here further investigation would be of interest.

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          Most cited references29

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          [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue].

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            Fertile ground: human endometrial programming and lessons in health and disease.

            The human endometrium is a highly dynamic tissue that is cyclically shed, repaired, regenerated and remodelled, primarily under the orchestration of oestrogen and progesterone, in preparation for embryo implantation. Humans are among the very few species that menstruate and that, consequently, are equipped with unique cellular and molecular mechanisms controlling these cyclic processes. Many reproductive pathologies are specific to menstruating species, and studies in animal models rarely translate to humans. Abnormal remodelling and regeneration of the human endometrium leads to a range of reproductive complications. Furthermore, the processes regulating endometrial remodelling and implantation, including those controlling hormonal impact, breakdown and repair, stem/progenitor cell activation, inflammation and cell invasion have broad applications to other fields. This Review presents current knowledge regarding the normal and abnormal function of the human endometrium. The development of biomarkers for prediction of uterine diseases and pregnancy disorders and future avenues of investigation to improve fertility and enhance endometrial function are also discussed.
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              Conditional deletion of Msx homeobox genes in the uterus inhibits blastocyst implantation by altering uterine receptivity.

              An effective bidirectional communication between an implantation-competent blastocyst and the receptive uterus is a prerequisite for mammalian reproduction. The blastocyst will implant only when this molecular cross-talk is established. Here we show that the muscle segment homeobox gene (Msh) family members Msx1 and Msx2, which are two highly conserved genes critical for epithelial-mesenchymal interactions during development, also play crucial roles in embryo implantation. Loss of Msx1/Msx2 expression correlates with altered uterine luminal epithelial cell polarity and affects E-cadherin/β-catenin complex formation through the control of Wnt5a expression. Application of Wnt5a in vitro compromised blastocyst invasion and trophoblast outgrowth on cultured uterine epithelial cells. The finding that Msx1/Msx2 genes are critical for conferring uterine receptivity and readiness to implantation could have clinical significance, because compromised uterine receptivity is a major cause of pregnancy failure in IVF programs. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                udo.jeschke@med.uni-muenchen.de
                Journal
                Arch Gynecol Obstet
                Arch Gynecol Obstet
                Archives of Gynecology and Obstetrics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0932-0067
                1432-0711
                27 April 2023
                27 April 2023
                2023
                : 308
                : 1
                : 273-279
                Affiliations
                [1 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Department of Obstetrics and Gynecology, , University Hospital, Ludwig Maximilians University (LMU), ; Marchioninistraße 15, 81377 Munich, Germany
                [2 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Department of Pathology, , LMU Munich, ; Thalkirchner Str. 56, 80337 Munich, Germany
                [3 ]GRID grid.419801.5, ISNI 0000 0000 9312 0220, Department of Obstetrics and Gynecology, , University Hospital Augsburg, ; Stenglinstr. 2, 86156 Augsburg, Germany
                [4 ]GRID grid.411984.1, ISNI 0000 0001 0482 5331, Department of Gynecology and Obstetrics, , Georg August University Göttingen, University Medicine, ; Göttingen, Germany
                Author information
                http://orcid.org/0000-0003-2623-3235
                Article
                7033
                10.1007/s00404-023-07033-5
                10192152
                37101223
                49ca1de0-871d-4221-b7a8-502e5ea36160
                © The Author(s) 2023

                Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 9 January 2023
                : 27 March 2023
                Funding
                Funded by: Universitätsklinik München (6933)
                Categories
                Gynecologic Endocrinology and Reproductive Medicine
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2023

                Obstetrics & Gynecology
                msx-1,progesterone receptor,endometrium,proliferative phase,glandular cells

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