Loss of MIG-6 results in endometrial progesterone resistance via ERBB2.
Date
2022-03
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Abstract
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 (Pgrcre/+Mig-6f/f; Mig-6d/d). To investigate the effect of ERBB2 targeting on endometrial progesterone resistance, fertility, and endometriosis, we introduce Erbb2 ablation in Mig-6d/d mice (Mig-6d/dErbb2d/d mice). The additional knockout of Erbb2 rescues all phenotypes seen in Mig-6d/d mice. Transcriptomic analysis shows that genes differentially expressed in Mig-6d/d mice revert to their normal expression in Mig-6d/dErbb2d/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.
Type
Department
Description
Provenance
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Yoo, Jung-Yoon, Tae Hoon Kim, Jung-Ho Shin, Ryan M Marquardt, Ulrich Müller, Asgerally T Fazleabas, Steven L Young, Bruce A Lessey, et al. (2022). Loss of MIG-6 results in endometrial progesterone resistance via ERBB2. Nature communications, 13(1). p. 1101. 10.1038/s41467-022-28608-x Retrieved from https://hdl.handle.net/10161/29060.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke
Steven L Young
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.