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Loss of MIG-6 results in endometrial progesterone resistance via ERBB2

Female subfertility is highly associated with endometriosis. Endometrial progesterone resistance is suggested as a crucial element in the development of endometrial diseases. We report that MIG-6 is downregulated in the endometrium of infertile women with endometriosis and in a non-human primate mod...

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Autores principales: Yoo, Jung-Yoon, Kim, Tae Hoon, Shin, Jung-Ho, Marquardt, Ryan M., Müller, Ulrich, Fazleabas, Asgerally T., Young, Steven L., Lessey, Bruce A., Yoon, Ho-Geun, Jeong, Jae-Wook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888616/
https://www.ncbi.nlm.nih.gov/pubmed/35232969
http://dx.doi.org/10.1038/s41467-022-28608-x
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author Yoo, Jung-Yoon
Kim, Tae Hoon
Shin, Jung-Ho
Marquardt, Ryan M.
Müller, Ulrich
Fazleabas, Asgerally T.
Young, Steven L.
Lessey, Bruce A.
Yoon, Ho-Geun
Jeong, Jae-Wook
author_facet Yoo, Jung-Yoon
Kim, Tae Hoon
Shin, Jung-Ho
Marquardt, Ryan M.
Müller, Ulrich
Fazleabas, Asgerally T.
Young, Steven L.
Lessey, Bruce A.
Yoon, Ho-Geun
Jeong, Jae-Wook
author_sort Yoo, Jung-Yoon
collection PubMed
description Female subfertility is highly associated with endometriosis. Endometrial progesterone resistance is suggested as a crucial element in the development of endometrial diseases. We report that MIG-6 is downregulated in the endometrium of infertile women with endometriosis and in a non-human primate model of endometriosis. We find ERBB2 overexpression in the endometrium of uterine-specific Mig-6 knockout mice (Pgr(cre/+)Mig-6(f/f); Mig-6(d/d)). To investigate the effect of ERBB2 targeting on endometrial progesterone resistance, fertility, and endometriosis, we introduce Erbb2 ablation in Mig-6(d/d) mice (Mig-6(d/d)Erbb2(d/d) mice). The additional knockout of Erbb2 rescues all phenotypes seen in Mig-6(d/d) mice. Transcriptomic analysis shows that genes differentially expressed in Mig-6(d/d) mice revert to their normal expression in Mig-6(d/d)Erbb2(d/d) mice. Together, our results demonstrate that ERBB2 overexpression in endometrium with MIG-6 deficiency causes endometrial progesterone resistance and a nonreceptive endometrium in endometriosis-related infertility, and ERBB2 targeting reverses these effects.
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spelling pubmed-88886162022-03-17 Loss of MIG-6 results in endometrial progesterone resistance via ERBB2 Yoo, Jung-Yoon Kim, Tae Hoon Shin, Jung-Ho Marquardt, Ryan M. Müller, Ulrich Fazleabas, Asgerally T. Young, Steven L. Lessey, Bruce A. Yoon, Ho-Geun Jeong, Jae-Wook Nat Commun Article Female subfertility is highly associated with endometriosis. Endometrial progesterone resistance is suggested as a crucial element in the development of endometrial diseases. We report that MIG-6 is downregulated in the endometrium of infertile women with endometriosis and in a non-human primate model of endometriosis. We find ERBB2 overexpression in the endometrium of uterine-specific Mig-6 knockout mice (Pgr(cre/+)Mig-6(f/f); Mig-6(d/d)). To investigate the effect of ERBB2 targeting on endometrial progesterone resistance, fertility, and endometriosis, we introduce Erbb2 ablation in Mig-6(d/d) mice (Mig-6(d/d)Erbb2(d/d) mice). The additional knockout of Erbb2 rescues all phenotypes seen in Mig-6(d/d) mice. Transcriptomic analysis shows that genes differentially expressed in Mig-6(d/d) mice revert to their normal expression in Mig-6(d/d)Erbb2(d/d) mice. Together, our results demonstrate that ERBB2 overexpression in endometrium with MIG-6 deficiency causes endometrial progesterone resistance and a nonreceptive endometrium in endometriosis-related infertility, and ERBB2 targeting reverses these effects. Nature Publishing Group UK 2022-03-01 /pmc/articles/PMC8888616/ /pubmed/35232969 http://dx.doi.org/10.1038/s41467-022-28608-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yoo, Jung-Yoon
Kim, Tae Hoon
Shin, Jung-Ho
Marquardt, Ryan M.
Müller, Ulrich
Fazleabas, Asgerally T.
Young, Steven L.
Lessey, Bruce A.
Yoon, Ho-Geun
Jeong, Jae-Wook
Loss of MIG-6 results in endometrial progesterone resistance via ERBB2
title Loss of MIG-6 results in endometrial progesterone resistance via ERBB2
title_full Loss of MIG-6 results in endometrial progesterone resistance via ERBB2
title_fullStr Loss of MIG-6 results in endometrial progesterone resistance via ERBB2
title_full_unstemmed Loss of MIG-6 results in endometrial progesterone resistance via ERBB2
title_short Loss of MIG-6 results in endometrial progesterone resistance via ERBB2
title_sort loss of mig-6 results in endometrial progesterone resistance via erbb2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888616/
https://www.ncbi.nlm.nih.gov/pubmed/35232969
http://dx.doi.org/10.1038/s41467-022-28608-x
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