Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews...
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • Allergy (Apr 2019)
    • Biology of familial cancer predisposition syndromes (Feb 2019)
    • Mitochondrial dysfunction in disease (Aug 2018)
    • Lipid mediators of disease (Jul 2018)
    • Cellular senescence in human disease (Apr 2018)
    • View all review series...
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Scientific Show Stoppers
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Current issue
  • Past issues
  • By specialty
  • Subscribe
  • Alerts
  • Advertise
  • Contact
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • Brief Reports
  • Technical Advances
  • Commentaries
  • Editorials
  • Hindsight
  • Review series
  • Reviews
  • The Attending Physician
  • First Author Perspectives
  • Scientific Show Stoppers
  • Top read articles
  • Concise Communication
Polycomb subunit BMI1 determines uterine progesterone responsiveness essential for normal embryo implantation
Qiliang Xin, … , Chao Wang, Haibin Wang
Qiliang Xin, … , Chao Wang, Haibin Wang
Published January 2, 2018; First published November 20, 2017
Citation Information: J Clin Invest. 2018;128(1):175-189. https://doi.org/10.1172/JCI92862.
View: Text | PDF
Categories: Research Article Reproductive biology

Polycomb subunit BMI1 determines uterine progesterone responsiveness essential for normal embryo implantation

  • Text
  • PDF
Abstract

Natural and synthetic progestogens have been commonly used to prevent recurrent pregnancy loss in women with inadequate progesterone secretion or reduced progesterone sensitivity. However, the clinical efficacy of progesterone and its analogs for maintaining pregnancy is variable. Additionally, the underlying cause of impaired endometrial progesterone responsiveness during early pregnancy remains unknown. Here, we demonstrated that uterine-selective depletion of BMI1, a key component of the polycomb repressive complex-1 (PRC1), hampers uterine progesterone responsiveness and derails normal uterine receptivity, resulting in implantation failure in mice. We further uncovered genetic and biochemical evidence that BMI1 interacts with the progesterone receptor (PR) and the E3 ligase E6AP in a polycomb complex–independent manner and regulates the PR ubiquitination that is essential for normal progesterone responsiveness. A close association of aberrantly low endometrial BMI1 expression with restrained PR responsiveness in women who had previously had a miscarriage indicated that the role of BMI1 in endometrial PR function is conserved in mice and in humans. In addition to uncovering a potential regulatory mechanism of BMI1 that ensures normal endometrial progesterone responsiveness during early pregnancy, our findings have the potential to help clarify the underlying causes of spontaneous pregnancy loss in women.

Authors

Qiliang Xin, Shuangbo Kong, Junhao Yan, Jingtao Qiu, Bo He, Chan Zhou, Zhangli Ni, Haili Bao, Lin Huang, Jinhua Lu, Guoliang Xia, Xicheng Liu, Zi-Jiang Chen, Chao Wang, Haibin Wang

×

Figure 9

Illustrative working model showing how uterine BMI1 is essential for optimal PR sensitivity and thus uterine receptivity at periimplantation.

Options: View larger image (or click on image) Download as PowerPoint
Illustrative working model showing how uterine BMI1 is essential for opt...
BMI1 interacts with PR and E6AP in a polycomb-independent manner, regulating PR ubiquitination essential for normal progesterone responsiveness. Uterine-selective depletion of BMI1 hampers uterine progesterone responsiveness and thus derails normal uterine receptivity, resulting in implantation failure. CoAs, coactivators.
Follow JCI:
Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts