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2. Effect of aging on the human myometrium at single-cell resolution

Author

Punzon-Jimenez, Paula, Machado-Lopez, Alba, Perez-Moraga, Raul, Llera-Oyola, Jaime, Grases, Daniela, Galvez-Viedma, Marta, Sibai, Mustafa, Satorres-Perez, Elena, Lopez-Agullo, Susana, Badenes, Rafael, Ferrer-Gomez, Carolina, Porta-Pardo, Eduard, Roson, Beatriz, Simon, Carlos, and Mas, Aymara

Published
2024
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5. Management of Uterine Fibroids and Sarcomas: The Palermo Position Paper

Author

Laganà, Antonio Simone, primary, Romano, Andrea, additional, Vanhie, Arne, additional, Bafort, Celine, additional, Götte, Martin, additional, Aaltonen, Lauri A., additional, Mas, Aymara, additional, De Bruyn, Christine, additional, Van den Bosch, Thierry, additional, Coosemans, An, additional, Guerriero, Stefano, additional, Haimovich, Sergio, additional, Tanos, Vasilios, additional, Bongers, Marlies, additional, Barra, Fabio, additional, Al-Hendy, Ayman, additional, Chiantera, Vito, additional, and Leone Roberti Maggiore, Umberto, additional

Published
2024
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6. SINGLE-CELL ATLAS OF THE AGING HUMAN MYOMETRIUM REVEALS IMPAIRED CONTRACTILITY

Author

Punzón-Jiménez, Paula, primary, Machado-Lopez, Alba, additional, Pérez-Moraga, Raul, additional, Oyola, Jaime Llera, additional, Mendoza, Daniela Grases, additional, Viedma, Marta Gálvez, additional, Satorres, Elena, additional, Gomez, Carolina Ferrer, additional, Badenes, Rafael, additional, Roson, Beatriz, additional, Porta, Eduard, additional, Simon, Carlos, additional, and Mas, Aymara, additional

Published
2023
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9. Uterine leiomyoma with RAD51B::NUDT3 fusion: a report of 2 cases

Author

Dundr, Pavel, primary, Machado-Lopez, Alba, additional, Mas, Aymara, additional, Věcková, Zuzana, additional, Mára, Michal, additional, Richtárová, Adéla, additional, Matěj, Radoslav, additional, Stružinská, Ivana, additional, Kendall Bártů, Michaela, additional, Němejcová, Kristýna, additional, Dvořák, Jiří, additional, and Hojný, Jan, additional

Published
2023
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14. THE HUMAN PERICONCEPTIONAL MATERNALE-MBRYONIC SPACE IN HEALTH AND DISEASE.

Author

Moreno, Inmaculada, Capalbo, Antonio, Mas, Aymara, Garrido-Gomez, Tamara, Roson, Beatriz, Poli, Maurizio, Dimitriadis, Eva, Santamaria, Xavier, Vilella, Felipe, and Simon, Carlos

Subjects
EMBRYO implantation, HUMAN embryos, DECIDUA, PLACENTA praevia, MYOMETRIUM, CHILDREN'S health
Abstract

Pregnancy is established during the periconceptional period as a continuum beginning with blastocyst attachment to the endometrial epithelial surface followed by embryo invasion and placenta formation. This period sets the foundation for the child and mother's health during pregnancy. Emerging evidence indicates that prevention of downstream pathologies in both the embryo/newborn and pregnant mother may be possible at this stage. In this review, we discuss current advances in the periconceptional space, including the preimplantation human embryo and maternal endometrium. We also discuss the role of the maternal decidua, the periconceptional maternal-embryonic interface, the dialogue between these elements, and the importance of the endometrial microbiome in the implantation process and pregnancy. Finally, we discuss the myometrium in the periconceptional space and review its role in determining pregnancy health. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Integrative Genomic and Transcriptomic Profiling Reveals a Differential Molecular Signature in Uterine Leiomyoma versus Leiomyosarcoma

Author

Machado-Lopez, Alba, primary, Alonso, Roberto, additional, Lago, Victor, additional, Jimenez-Almazan, Jorge, additional, Garcia, Marta, additional, Monleon, Javier, additional, Lopez, Susana, additional, Barcelo, Francisco, additional, Torroba, Amparo, additional, Ortiz, Sebastian, additional, Domingo, Santiago, additional, Simon, Carlos, additional, and Mas, Aymara, additional

Published
2022
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26. Updated approaches for management of uterine fibroids

Author

Mas,Aymara, Tarazona,Marta, Dasí Carrasco,Joana, Estaca,Gloria, Cristóbal,Ignacio, and Monleón,Javier

Subjects
International Journal of Women's Health
Abstract

Aymara Mas,1,2 Marta Tarazona,3 Joana Dasí Carrasco,3 Gloria Estaca,4,5 Ignacio Cristóbal,4,5 Javier Monleón3 1Reproductive Medicine Research Group, Institute of Health Research La Fe, University and Polytechnic Hospital La Fe, Valencia, Spain; 2Research and Development Department, Igenomix Foundation, Valencia, Spain; 3Gynecology Department, University and Polytechnic Hospital La Fe, Valencia, Spain; 4Obstetrics and Gynecology Department, La Zarzuela Hospital, Madrid, Spain; 5Obstetrics and Gynecology Department, Universidad Francisco de Vitoria, Madrid, Spain Abstract: Uterine anatomy and uterine fibroids (UFs) characteristics have been classically considered as almost a unique issue in gynecology and reproductive medicine. Nowadays, the management of UF pathology is undergoing an important evolution, with the patient’s quality of life being the most important aspect to consider. Accordingly, surgical techniques and aggressive treatments are reserved for only those cases with heavy symptomatology, while the clinical diagnostic based on size and number of UFs remains in a second plane in these situations. Moreover, the development of several noninvasive surgical techniques, especially the appearance of ulipristal acetate as a medical etiological treatment, has substantially changed the clinical indications. As a consequence, after almost 2 decades without relevant updates, it has been necessary to update the protocols for the management of UFs in the Spanish Society of Gynecology and Obstetrics twice. Accordingly, we believe that it is necessary to translate our experience to protocolize the medical care for patients with UFs, incorporating these new therapeutic options, and selecting the best treatment for them. We highlight the importance of achieving the patient’s goals and decisions by improving the clinical diagnosis for these type of pathologies, allowing enhanced personalized treatments, as well as the reduction of potential risks and unnecessary surgeries. Keywords: uterine fibroids, UFs, selective progesterone receptor modulator, sPRM, ulipristal acetate, UPA

Published
2017

32. Molecular differential diagnosis of uterine leiomyomas and leiomyosarcomas.

Author

Mas, Aymara and Simón, Carlos

Abstract

Uterine leiomyomas (LM) and leiomyosarcomas (LMS) are considered biologically unrelated tumors due to their cytogenetic and molecular disparity. Yet, these tumors share morphological and molecular characteristics that cannot be differentiated through current clinical diagnostic tests, and thus cannot be definitively classified as benign or malignant until surgery. Newer approaches are needed for the identification of these tumors, as has been done for other tissues. The application of next generation sequencing enables the detection of new mutations that, when coupled to machine learning bioinformatic tools, advances our understanding of chromosomal instability. These approaches in the context of LM and LMS could allow the discovery of genetic variants and possible genomic markers. Additionally, the potential clinical utility of circulating cell-free tumor DNA could revolutionize the noninvasive detection and monitoring of these tumors. Here, we seek to provide a perspective on the molecular background of LM and LMS, recognizing their distinct molecular features that may lead to improved diagnosis and personalized treatments, which would have a measurable impact on women's reproductive health.

Published
2019
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35. Developmental Exposure to Endocrine Disruptors Expands Murine Myometrial Stem Cell Compartment as a Prerequisite to Leiomyoma Tumorigenesis.

Author

Mas, Aymara, Stone, Leyland, O'Connor, Paul M., Yang, Qiwei, Kleven, Daniel, Simon, Carlos, Walker, Cheryl L., and Al-Hendy, Ayman

Abstract

A bstract Despite the high prevalence and major negative impact of uterine fibroids (UFs) on women's health, their pathogenesis remains largely unknown. While tumor-initiating cells have been previously isolated from UFs, the cell of origin for these tumors in normal myometrium has not been identified. We isolated cells with Stro1/CD44 surface markers from normal myometrium expressing stem cell markers Oct-4/c-kit/nanog that exhibited the properties of myometrial stem/progenitor-like cells (MSCs). Using a murine model for UFs, we showed that the cervix was a hypoxic 'niche' and primary site (96%) for fibroid development in these animals. The pool size of these MSCs also responded to environmental cues, contracting with age and expanding in response to developmental environmental exposures that promote fibroid development. Translating these findings to women, the number of MSCs in unaffected human myometrium correlated with risk for developing UFs. Caucasian (CC) women with fibroids had increased numbers of MSCs relative to CC women without fibroids, and African-American (AA) women at highest risk for these tumors had the highest number of MSCs: AA-with fibroids > CC-with fibroids > AA-without fibroids > CC-without fibroids. These data identify Stro1+/CD44+ MSCs as MSC/progenitor cell for UFs, and a target for ethnic and environmental factors that increase UF risk. S tem C ells 2017;35:666-678 [ABSTRACT FROM AUTHOR]

Published
2017
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40. Role of Stro1+/CD44+stem cells in myometrial physiology and uterine remodeling during pregnancy†

Author

Mas, Aymara, Prusinski, Lauren, Yang, Qiwei, Diaz-Gimeno, Patricia, Stone, Lelyand, Diamond, Michael P, Simón, Carlos, and Al-Hendy, Ayman

Abstract

Regulation of myometrial functions during pregnancy has been considered the result of the integration of endocrine and mechanical signals. Nevertheless, uterine regeneration is poorly understood, and the cellular source within the gravid uterus is largely unexplored.In this study, we isolated and quantified the myometrial stem cells (MSC) population from pregnant female Eker rat uteri, by using Stro1/CD44 surface markers. We demonstrated that prior parity significantly increased the percentage of Stro1+/CD44+MSC because of injured tissue response. Interestingly, we established that Stro1+/CD44+MSC respond efficiently to physiological cues when they were treated in vitro under different dose-dependent pregnant rat serum.Previous studies reveal strong regulatory links between O2availability and stem cell function. Based on these premises, cell proliferation assays showed that isolated Stro1+/CD44+MSC possess a higher proliferative rate under hypoxic versus normoxic conditions. We also detected a total of 37 upregulated and 44 downregulated hypoxia-related genes, which were differentially expressed in Stro1+/CD44+MSC, providing an alternative approach to infer into complex molecular mechanisms such as energy metabolism, inflammatory response, uterine expansion, and/or remodeling.Since these cells preferentially grow under low oxygen conditions, we propose that the increase of the rat uterus during pregnancy involves myometrial oxygen consumption, thereby enhancing MSC proliferation. Moreover, pregnancy-induced mechanical stretching results in hypoxic conditions, ultimately creating an environment that promotes stem cell proliferation and further uterine enlargement, which is essential for a successful pregnancy. In summary, all of these data support that rat Stro1+/CD44+MSC contribute to uterine enlargement during pregnancy.The human and murine uterus exhibits a large expansion in size and remodeling over the course of pregnancy. However, at this stage, little is known about the uterine regeneration at cellular level.Due to limited access to sequentially-timed human pregnant myometrial tissues, we proceeded to address these pivotal questions by using a rat animal model. In this study, we identified and characterized myometrial stem cells (MSC) from pregnant female Eker rat uteri, by using specific surface markers. We also demonstrated their contribution to uterine enlargement during pregnancy under hypoxic conditions. Nevertheless, further studies are needed to elucidate the exact role of myometrial stem cells in healthy pregnancy and also in pathological conditions such as preterm labor.

Published
2017
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42. Human Endometrial Side Population Cells Exhibit Genotypic, Phenotypic and Functional Features of Somatic Stem Cells

Author

Cervelló, Irene, primary, Gil-Sanchis, Claudia, additional, Mas, Aymara, additional, Delgado-Rosas, Francisco, additional, Martínez-Conejero, José Antonio, additional, Galán, Amparo, additional, Martínez-Romero, Alicia, additional, Martínez, Sebastian, additional, Navarro, Ismael, additional, Ferro, Jaime, additional, Horcajadas, José Antonio, additional, Esteban, Francisco José, additional, O'Connor, José Enrique, additional, Pellicer, Antonio, additional, and Simón, Carlos, additional

Published
2010
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43. Human Endometrial Side Population Cells Exhibit Genotypic, Phenotypic and Functional Features of Somatic Stem Cells.

Author

Irene Cervelló, Gil-Sanchis, Claudia, Mas, Aymara, Delgado-Rosas, Francisco, Marténez-Conejero, José Antonio, Galán, Amparo, Martínez-Romero, Alicia, Martínez, Sebastian, Navarro, Ismael, Ferro, Jaime, Horcajadas, José Antonio, Esteban, Francisco José, O'Connor, José Enrique, Pellicer, Antonio, and Simó n, Carlos

Subjects
STEM cells, ENDOMETRIUM physiology, HUMAN reproduction, REGENERATION (Biology), REGENERATIVE medicine, TELOMERASE, PHENOTYPES, PATHOLOGY
Abstract

During reproductive life, the human endometrium undergoes around 480 cycles of growth, breakdown and regeneration should pregnancy not be achieved. This outstanding regenerative capacity is the basis for women's cycling and its dysfunction may be involved in the etiology of pathological disorders. Therefore, the human endometrial tissue must rely on a remarkable endometrial somatic stem cells (SSC) population. Here we explore the hypothesis that human endometrial side population (SP) cells correspond to somatic stem cells. We isolated, identified and characterized the SP corresponding to the stromal and epithelial compartments using endometrial SP genes signature, immunophenotyping and characteristic telomerase pattern. We analyzed the clonogenic activity of SP cells under hypoxic conditions and the differentiation capacity in vitro to adipogenic and osteogenic lineages. Finally, we demonstrated the functional capability of endometrial SP to develop human endometrium after subcutaneous injection in NOD-SCID mice. Briefly, SP cells of human endometrium from epithelial and stromal compartments display genotypic, phenotypic and functional features of SSC. [ABSTRACT FROM AUTHOR]

Published
2010
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45. Overexpression of the truncated form of High Mobility Group A proteins (HMGA2) in human myometrial cells induces leiomyoma-like tissue formation.

Author

Mas A, Cervelló I, Fernández-Álvarez A, Faus A, Díaz A, Burgués O, Casado M, and Simón C

Subjects
Animals, Cell Transformation, Neoplastic metabolism, Cell Transformation, Neoplastic pathology, Exons, Female, HMGA2 Protein metabolism, Humans, Introns, Leiomyoma metabolism, Leiomyoma pathology, Mice, Mice, Inbred NOD, Mice, SCID, Myocytes, Smooth Muscle metabolism, Myocytes, Smooth Muscle pathology, Myocytes, Smooth Muscle transplantation, Myometrium pathology, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Plasmids chemistry, Plasmids metabolism, Protein Isoforms genetics, Protein Isoforms metabolism, Stem Cells metabolism, Stem Cells pathology, Transfection, Transplantation, Heterologous, Uterine Neoplasms metabolism, Uterine Neoplasms pathology, Cell Transformation, Neoplastic genetics, Gene Expression Regulation, Neoplastic, HMGA2 Protein genetics, Leiomyoma genetics, Myometrium metabolism, Uterine Neoplasms genetics
Abstract

The pathogenesis of uterine leiomyomas, the most common benign tumor in women, is still unknown. This lack of basic knowledge limits the development of novel non-invasive therapies. Our group has previously demonstrated that leiomyoma side population (SP) cells are present in tumor lesions and act like putative tumor-initiating stem cells in human leiomyoma. Moreover, accumulated evidence demonstrates that these benign tumors of mesenchymal origin are characterized by rearrangements of the High Mobility Group A proteins (HMGA). In this work, we tested the hypothesis that leiomyoma development may be due to overexpression of HMGA2 (encoding high mobility group AT-hook2) in myometrial stem cells using in vitro and in vivo approaches. Our work demonstrates that the truncated/short form of HMGA2 induces myometrial cell transformation toward putative tumor-initiating leiomyoma cells and opens up new possibilities to understand the origin of leiomyomas and the development of new therapeutic approaches., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Published
2015
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