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The ontogeny of myometrial stem cells in OCT4-GFP transgenic mouse model

BACKGROUND: Myometrium, the muscular wall of the uterus, is an active organ markedly remodeled during a woman’s reproductive life, especially during pregnancy. Different studies using the 5-bromo-2′-deoxyuridine and side population methods in murine and human myometrium have suggested the presence o...

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Autores principales: Brakta, Soumia, Mas, Aymara, Al-Hendy, Ayman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264618/
https://www.ncbi.nlm.nih.gov/pubmed/30486855
http://dx.doi.org/10.1186/s13287-018-1079-7
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author Brakta, Soumia
Mas, Aymara
Al-Hendy, Ayman
author_facet Brakta, Soumia
Mas, Aymara
Al-Hendy, Ayman
author_sort Brakta, Soumia
collection PubMed
description BACKGROUND: Myometrium, the muscular wall of the uterus, is an active organ markedly remodeled during a woman’s reproductive life, especially during pregnancy. Different studies using the 5-bromo-2′-deoxyuridine and side population methods in murine and human myometrium have suggested the presence of somatic stem cells in this tissue because of its remarkable regenerative capacity. Recently, our group has developed a surface-marker (Stro1/CD44)-specific approach to isolate and characterize myometrial somatic stem cells (SSCs) from humans and rats. OBJECTIVE: In this study, we aimed to identify and localize the putative myometrial stem cell population in the murine uterus by using the specific surface markers, Nanog/CD44. METHODS: Uteri from OCT4-GFP transgenic mice at different early-life time points were analyzed via single and double immunohistochemistry to co-localize myometrial stem cell marker CD44 with other general stemmness markers, e.g., Nanog and Oct-4. Finally, we correlated the frequency of myometrial stem cells in vivo with the expression of sex steroid hormone receptors, estrogen receptor α (ERα), and progesterone receptors A and B (PR A&B). RESULTS: Nanog(+)/CD44(+) stem cells were present in murine myometrium. Both stem cell markers were shown to co-localize with Oct-4 expression. Time-course experiments demonstrated that their percentages were significantly lower at the pre-sexual age of 1 week than at the sexually mature ages of 3 to 24 weeks. Importantly, both ERα and PR A&B were abundantly expressed in the myometrium at ages 1, 3 and 4 weeks. CONCLUSIONS: We demonstrated that murine CD44(+) myometrial cells have features of somatic stem cells with the expression of typical undifferentiated markers. Furthermore, our results suggest that myometrial stem cells are sex steroid hormone dependent, likely via paracrine pathway, and increase in numbers with reproductive maturity and rise in serum estrogen and progesterone levels around 3 weeks of age in mice. The abundance and early onset expression of ER/PR emphasize the vulnerability of neonatal myometrium to environmental endocrine disruptors which can potentially lead to permanent reprograming and adult onset of myometrial disorders such as uterine fibroids. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-018-1079-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-62646182018-12-05 The ontogeny of myometrial stem cells in OCT4-GFP transgenic mouse model Brakta, Soumia Mas, Aymara Al-Hendy, Ayman Stem Cell Res Ther Research BACKGROUND: Myometrium, the muscular wall of the uterus, is an active organ markedly remodeled during a woman’s reproductive life, especially during pregnancy. Different studies using the 5-bromo-2′-deoxyuridine and side population methods in murine and human myometrium have suggested the presence of somatic stem cells in this tissue because of its remarkable regenerative capacity. Recently, our group has developed a surface-marker (Stro1/CD44)-specific approach to isolate and characterize myometrial somatic stem cells (SSCs) from humans and rats. OBJECTIVE: In this study, we aimed to identify and localize the putative myometrial stem cell population in the murine uterus by using the specific surface markers, Nanog/CD44. METHODS: Uteri from OCT4-GFP transgenic mice at different early-life time points were analyzed via single and double immunohistochemistry to co-localize myometrial stem cell marker CD44 with other general stemmness markers, e.g., Nanog and Oct-4. Finally, we correlated the frequency of myometrial stem cells in vivo with the expression of sex steroid hormone receptors, estrogen receptor α (ERα), and progesterone receptors A and B (PR A&B). RESULTS: Nanog(+)/CD44(+) stem cells were present in murine myometrium. Both stem cell markers were shown to co-localize with Oct-4 expression. Time-course experiments demonstrated that their percentages were significantly lower at the pre-sexual age of 1 week than at the sexually mature ages of 3 to 24 weeks. Importantly, both ERα and PR A&B were abundantly expressed in the myometrium at ages 1, 3 and 4 weeks. CONCLUSIONS: We demonstrated that murine CD44(+) myometrial cells have features of somatic stem cells with the expression of typical undifferentiated markers. Furthermore, our results suggest that myometrial stem cells are sex steroid hormone dependent, likely via paracrine pathway, and increase in numbers with reproductive maturity and rise in serum estrogen and progesterone levels around 3 weeks of age in mice. The abundance and early onset expression of ER/PR emphasize the vulnerability of neonatal myometrium to environmental endocrine disruptors which can potentially lead to permanent reprograming and adult onset of myometrial disorders such as uterine fibroids. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-018-1079-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-29 /pmc/articles/PMC6264618/ /pubmed/30486855 http://dx.doi.org/10.1186/s13287-018-1079-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Brakta, Soumia
Mas, Aymara
Al-Hendy, Ayman
The ontogeny of myometrial stem cells in OCT4-GFP transgenic mouse model
title The ontogeny of myometrial stem cells in OCT4-GFP transgenic mouse model
title_full The ontogeny of myometrial stem cells in OCT4-GFP transgenic mouse model
title_fullStr The ontogeny of myometrial stem cells in OCT4-GFP transgenic mouse model
title_full_unstemmed The ontogeny of myometrial stem cells in OCT4-GFP transgenic mouse model
title_short The ontogeny of myometrial stem cells in OCT4-GFP transgenic mouse model
title_sort ontogeny of myometrial stem cells in oct4-gfp transgenic mouse model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264618/
https://www.ncbi.nlm.nih.gov/pubmed/30486855
http://dx.doi.org/10.1186/s13287-018-1079-7
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