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Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal

Myometrium cells are an important reproductive niche in which cyclic mechanical forces of a pico-newton range are produced continuously at millisecond and second intervals. Overproduction and/or underproduction of micro-forces, due to point or epigenetic mutation, aberrant methylation, and abnormal...

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Autores principales: Celik, Onder, Celik, Nilufer, Gungor, Nur Dokuzeylul, Celik, Sudenaz, Arslan, Liya, Morciano, Andrea, Tinelli, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692870/
https://www.ncbi.nlm.nih.gov/pubmed/36430682
http://dx.doi.org/10.3390/ijms232214201
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author Celik, Onder
Celik, Nilufer
Gungor, Nur Dokuzeylul
Celik, Sudenaz
Arslan, Liya
Morciano, Andrea
Tinelli, Andrea
author_facet Celik, Onder
Celik, Nilufer
Gungor, Nur Dokuzeylul
Celik, Sudenaz
Arslan, Liya
Morciano, Andrea
Tinelli, Andrea
author_sort Celik, Onder
collection PubMed
description Myometrium cells are an important reproductive niche in which cyclic mechanical forces of a pico-newton range are produced continuously at millisecond and second intervals. Overproduction and/or underproduction of micro-forces, due to point or epigenetic mutation, aberrant methylation, and abnormal response to hypoxia, may lead to the transformation of fibroid stem cells into fibroid-initiating stem cells. Fibroids are tumors with a high modulus of stiffness disturbing the critical homeostasis of the myometrium and they may cause unfavorable and strong mechanical forces. Micro-mechanical forces and soluble-chemical signals play a critical role in transcriptional and translational processes’ maintenance, by regulating communication between the cell nucleus and its organelles. Signals coming from the external environment can stimulate cells in the format of both soluble biochemical signals and mechanical ones. The shape of the cell and the plasma membrane have a significant character in sensing electro-chemical signals, through specialized receptors and generating responses, accordingly. In order for mechanical signals to be perceived by the cell, they must be converted into biological stimuli, through a process called mechanotransduction. Transmission of fibroid-derived mechanical signals to the endometrium and their effects on receptivity modulators are mediated through a pathway known as solid-state signaling. It is not sufficiently clear which type of receptors and mechanical signals impair endometrial receptivity. However, it is known that biomechanical signals reaching the endometrium affect epithelial sodium channels, lysophosphatidic acid receptors or Rho GTPases, leading to conformational changes in endometrial proteins. Translational changes in receptivity modulators may disrupt the selectivity and receptivity functions of the endometrium, resulting in failed implantation or early pregnancy loss. By hypermethylation of the receptivity genes, micro-forces can also negatively affect decidualization and implantation. The purpose of this narrative review is to summarize the state of the art of the biomechanical forces which can determine fibroid stem cell transformation and, thus, affect the receptivity status of the endometrium with regard to fertilization and pregnancy.
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spelling pubmed-96928702022-11-26 Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal Celik, Onder Celik, Nilufer Gungor, Nur Dokuzeylul Celik, Sudenaz Arslan, Liya Morciano, Andrea Tinelli, Andrea Int J Mol Sci Review Myometrium cells are an important reproductive niche in which cyclic mechanical forces of a pico-newton range are produced continuously at millisecond and second intervals. Overproduction and/or underproduction of micro-forces, due to point or epigenetic mutation, aberrant methylation, and abnormal response to hypoxia, may lead to the transformation of fibroid stem cells into fibroid-initiating stem cells. Fibroids are tumors with a high modulus of stiffness disturbing the critical homeostasis of the myometrium and they may cause unfavorable and strong mechanical forces. Micro-mechanical forces and soluble-chemical signals play a critical role in transcriptional and translational processes’ maintenance, by regulating communication between the cell nucleus and its organelles. Signals coming from the external environment can stimulate cells in the format of both soluble biochemical signals and mechanical ones. The shape of the cell and the plasma membrane have a significant character in sensing electro-chemical signals, through specialized receptors and generating responses, accordingly. In order for mechanical signals to be perceived by the cell, they must be converted into biological stimuli, through a process called mechanotransduction. Transmission of fibroid-derived mechanical signals to the endometrium and their effects on receptivity modulators are mediated through a pathway known as solid-state signaling. It is not sufficiently clear which type of receptors and mechanical signals impair endometrial receptivity. However, it is known that biomechanical signals reaching the endometrium affect epithelial sodium channels, lysophosphatidic acid receptors or Rho GTPases, leading to conformational changes in endometrial proteins. Translational changes in receptivity modulators may disrupt the selectivity and receptivity functions of the endometrium, resulting in failed implantation or early pregnancy loss. By hypermethylation of the receptivity genes, micro-forces can also negatively affect decidualization and implantation. The purpose of this narrative review is to summarize the state of the art of the biomechanical forces which can determine fibroid stem cell transformation and, thus, affect the receptivity status of the endometrium with regard to fertilization and pregnancy. MDPI 2022-11-17 /pmc/articles/PMC9692870/ /pubmed/36430682 http://dx.doi.org/10.3390/ijms232214201 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Celik, Onder
Celik, Nilufer
Gungor, Nur Dokuzeylul
Celik, Sudenaz
Arslan, Liya
Morciano, Andrea
Tinelli, Andrea
Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal
title Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal
title_full Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal
title_fullStr Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal
title_full_unstemmed Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal
title_short Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal
title_sort biomechanical forces determine fibroid stem cell transformation and the receptivity status of the endometrium: a critical appraisal
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692870/
https://www.ncbi.nlm.nih.gov/pubmed/36430682
http://dx.doi.org/10.3390/ijms232214201
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