IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28608-x.html
   My bibliography  Save this article

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

Author

Listed:
  • Jung-Yoon Yoo

    (Michigan State University, College of Human Medicine
    Yonsei University Mirae Campus)

  • Tae Hoon Kim

    (Michigan State University, College of Human Medicine)

  • Jung-Ho Shin

    (Guro Hospital, Korea University Medical Center)

  • Ryan M. Marquardt

    (Michigan State University, College of Human Medicine
    Michigan State University)

  • Ulrich Müller

    (Johns Hopkins University School of Medicine)

  • Asgerally T. Fazleabas

    (Michigan State University, College of Human Medicine)

  • Steven L. Young

    (University of North Carolina)

  • Bruce A. Lessey

    (Wake Forest Baptist Health)

  • Ho-Geun Yoon

    (Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine)

  • Jae-Wook Jeong

    (Michigan State University, College of Human Medicine)

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.

Suggested Citation

  • Jung-Yoon Yoo & Tae Hoon Kim & Jung-Ho Shin & Ryan M. Marquardt & Ulrich Müller & Asgerally T. Fazleabas & Steven L. Young & Bruce A. Lessey & Ho-Geun Yoon & Jae-Wook Jeong, 2022. "Loss of MIG-6 results in endometrial progesterone resistance via ERBB2," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28608-x
    DOI: 10.1038/s41467-022-28608-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28608-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-28608-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Xuewu Zhang & Kerry A. Pickin & Ron Bose & Natalia Jura & Philip A. Cole & John Kuriyan, 2007. "Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface," Nature, Nature, vol. 450(7170), pages 741-744, November.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Mihaela Pavličev & Caitlin E. McDonough-Goldstein & Andreja Moset Zupan & Lisa Muglia & Yueh-Chiang Hu & Fansheng Kong & Nagendra Monangi & Gülay Dagdas & Nina Zupančič & Jamie Maziarz & Debora Sinner, 2024. "A common allele increases endometrial Wnt4 expression, with antagonistic implications for pregnancy, reproductive cancers, and endometriosis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.

      More about this item

      Statistics

      Access and download statistics

      Corrections

      All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28608-x. See general information about how to correct material in RePEc.

      If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

      If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

      If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

      For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

      Please note that corrections may take a couple of weeks to filter through the various RePEc services.

      IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.