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MSX1 在健康人子宫内膜不同阶段的表达。

MSX1-expression during the different phases in healthy human endometrium.

机构信息

Department of Obstetrics and Gynecology, University Hospital, Ludwig Maximilians University (LMU), Marchioninistraße 15, 81377, Munich, Germany.

Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstr. 2, 86156, Augsburg, Germany.

出版信息

Arch Gynecol Obstet. 2023 Jul;308(1):273-279. doi: 10.1007/s00404-023-07033-5. Epub 2023 Apr 27.


DOI:10.1007/s00404-023-07033-5
PMID:37101223
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10192152/
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.

摘要

目的:人类子宫内膜由不同的层(基底层和功能层)组成,并在整个月经周期中经历不同的阶段。在之前的一篇论文中,我们的研究小组能够将 MSX1 描述为子宫内膜癌的一个阳性预后因子。本研究的目的是在不同阶段检查健康子宫内膜组织中的 MSX1 表达,以更深入地了解 MSX 在女性生殖系统中的调节机制。

材料和方法:在这项回顾性研究中,我们共研究了 17 例正常子宫内膜组织(增殖期 6 例,早期分泌期 5 例,晚期分泌期 6 例)。我们使用免疫组织化学染色和免疫反应评分(IRS)来评估 MSX1 的表达。我们还研究了与我们的研究小组使用相同患者群体已经检查过的其他蛋白质的相关性。

结果:MSX1 在增殖期的腺体细胞中表达,并在早期和晚期分泌期下调(p=0.011)。此外,还发现 MSX1 与孕激素受体 A(PR-A)(相关系数(cc)=0.0671;p=0.024)和孕激素受体 B(PR-B)(cc=0.0691;p=0.018)呈正相关。MSX1 与腺细胞中抑制素β-C 表达之间呈负相关趋势(cc=-0.583;p 值=0.060)。

结论:MSX1 是肌肉节同源盒基因家族的成员之一。MSX1 是 p53 相互作用蛋白,同源盒 MSX1 的过表达诱导癌细胞凋亡。在这里,我们表明 MSX1 在正常子宫内膜的腺体上皮组织的增殖期表达特别明显。MSX1 与孕激素受体 A 和 B 之间的阳性相关性证实了我们的研究小组之前在癌症组织上的研究结果。因为 MSX1 已知被孕激素下调,所以 MSX1 与 PR-A 和 -B 之间的相关性可能代表 PR 反应元件对 MSX1 基因的直接调节。在这里,进一步的研究将是有趣的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f04/10192152/1e4e1952cb0f/404_2023_7033_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f04/10192152/4d871539491f/404_2023_7033_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f04/10192152/3d8703555164/404_2023_7033_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f04/10192152/1e4e1952cb0f/404_2023_7033_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f04/10192152/4d871539491f/404_2023_7033_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f04/10192152/3d8703555164/404_2023_7033_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f04/10192152/1e4e1952cb0f/404_2023_7033_Fig3_HTML.jpg

相似文献

[1]
MSX1-expression during the different phases in healthy human endometrium.

Arch Gynecol Obstet. 2023-7

[2]
Reduced homeobox protein MSX1 in human endometrial tissue is linked to infertility.

Hum Reprod. 2016-9

[3]
Expression of progesterone receptor mRNA in the endometrium during the normal menstrual cycle and in Norplant users.

Hum Reprod. 1996-12

[4]
P-glycoprotein expression is increased in human secretory and gestational endometrium.

Lab Invest. 1991-11

[5]
Apoptosis-related proteins and steroid hormone receptors in normal, hyperplastic, and neoplastic endometrium.

Int J Gynecol Pathol. 2002-10

[6]
Subnuclear distribution of progesterone receptors A and B in normal and malignant endometrium.

J Clin Endocrinol Metab. 2004-3

[7]
Immunohistochemical analysis of estrogen receptor alpha, estrogen receptor beta and progesterone receptor in normal human endometrium.

Acta Histochem. 2004

[8]
[Expression of ER and PR in the endometrium of patients with intrauterine adhesions].

Zhonghua Fu Chan Ke Za Zhi. 2017-1-25

[9]
Normal and malignant human endometrium express immunohistochemically estrogen receptor alpha (ER-alpha), estrogen receptor beta (ER-beta) and progesterone receptor (PR).

Anticancer Res. 2005

[10]
Oestrogen and progesterone receptors in the marmoset endometrium: changes during the ovulatory cycle, early pregnancy and after inhibition of vascular endothelial growth factor, GnRH or ovariectomy.

Reproduction. 2007-8

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[2]
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本文引用的文献

[1]
Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice.

Elife. 2022-7-21

[2]
Development of Potential Prognostic Biomarkers Based on DNA Methylation-Driven Genes for Patients with Endometrial Cancer.

Int J Gen Med. 2021-12-31

[3]
Identification and Validation of MSX1 as a Key Candidate for Progestin Resistance in Endometrial Cancer.

Onco Targets Ther. 2020-11-13

[4]
MSX1-A Potential Marker for Uterus-Preserving Therapy of Endometrial Carcinomas.

Int J Mol Sci. 2020-6-25

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Reprint of: Dating the Endometrial Biopsy.

Fertil Steril. 2019-10

[6]
Next generation sequencing reveals a novel nonsense mutation in MSX1 gene related to oligodontia.

PLoS One. 2018-9-7

[7]
induces G0/G1 arrest and apoptosis by suppressing Notch signaling and is frequently methylated in cervical cancer.

Onco Targets Ther. 2018-8-10

[8]
Homeobox protein MSX1 inhibits the growth and metastasis of breast cancer cells and is frequently silenced by promoter methylation.

Int J Mol Med. 2018-2-7

[9]
Growth factors FGF8 and FGF2 and their receptor FGFR1, transcriptional factors Msx-1 and MSX-2, and apoptotic factors p19 and RIP5 participate in the early human limb development.

Acta Histochem. 2018-4

[10]
Fertile ground: human endometrial programming and lessons in health and disease.

Nat Rev Endocrinol. 2016-7-22

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