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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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/14201 |
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| author | Onder Celik Nilufer Celik Nur Dokuzeylul Gungor Sudenaz Celik Liya Arslan Andrea Morciano Andrea Tinelli |
| author_facet | Onder Celik Nilufer Celik Nur Dokuzeylul Gungor Sudenaz Celik Liya Arslan Andrea Morciano Andrea Tinelli |
| author_sort | Onder Celik |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T18:16:53Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:16:53Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a347fc67efba40a8acccea4f83d3b4442023-11-24T08:40:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221420110.3390/ijms232214201Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical AppraisalOnder Celik0Nilufer Celik1Nur Dokuzeylul Gungor2Sudenaz Celik3Liya Arslan4Andrea Morciano5Andrea Tinelli6Department of Obstetrics and Gynecology, Private Clinic, Usak 64000, TurkeyDepartment of Biochemistry, Behcet Uz Children’s Hospital, Izmir 35210, TurkeyDepartment of Obstetrics and Gynecology, School of Medicine, Bahcesehir University, Istanbul 34732, TurkeyMedical Faculty, Sofia University “St. Kliment Ohridski”, 1407 Sofia, BulgariaMedical Faculty, Medical University of Sofia, 1431 Sofia, BulgariaDepartment of Obstetrics and Gynecology, “Cardinal Panico” General Hospital, 73020 Lecce, ItalyDepartment of Obstetrics and Gynecology and CERICSAL (Centro di RIcerca Clinica SALentino), “Veris Delli Ponti Hospital”, 73020 Lecce, ItalyMyometrium 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.https://www.mdpi.com/1422-0067/23/22/14201uterine fibroidfibroid stem cellsendometriummechanotransductionmicro-mechanical forcesendometrial receptivity |
| spellingShingle | Onder Celik Nilufer Celik Nur Dokuzeylul Gungor Sudenaz Celik Liya Arslan Andrea Morciano Andrea Tinelli Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal International Journal of Molecular Sciences uterine fibroid fibroid stem cells endometrium mechanotransduction micro-mechanical forces endometrial receptivity |
| 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 | uterine fibroid fibroid stem cells endometrium mechanotransduction micro-mechanical forces endometrial receptivity |
| url | https://www.mdpi.com/1422-0067/23/22/14201 |
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