Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Stromal Pbrm1 mediates chromatin remodeling necessary for embryo implantation in the mouse uterus
Qiliang Xin, … , Guoyun Yu, Jurrien Dean
Qiliang Xin, … , Guoyun Yu, Jurrien Dean
Published March 1, 2024
Citation Information: J Clin Invest. 2024;134(5):e174194. https://doi.org/10.1172/JCI174194.
View: Text | PDF
Research Article Endocrinology Reproductive biology

Stromal Pbrm1 mediates chromatin remodeling necessary for embryo implantation in the mouse uterus

  • Text
  • PDF
Abstract

Early gestational loss occurs in approximately 20% of all clinically recognized human pregnancies and is an important cause of morbidity. Either embryonic or maternal defects can cause loss, but a functioning and receptive uterine endometrium is crucial for embryo implantation. We report that the switch/sucrose nonfermentable (SWI/SNF) remodeling complex containing polybromo-1 (PBRM1) and Brahma-related gene 1 (BRG1) is essential for implantation of the embryonic blastocyst on the wall of the uterus in mice. Although preimplantation development is unaffected, conditional ablation of Pbrm1 in uterine stromal cells disrupts progesterone pathways and uterine receptivity. Heart and neural crest derivatives expressed 2 (Hand2) encodes a basic helix-loop-helix (bHLH) transcription factor required for embryo implantation. We identify an enhancer of the Hand2 gene in stromal cells that requires PBRM1 for epigenetic histone modifications/coactivator recruitment and looping with the promoter. In Pbrm1cKO mice, perturbation of chromatin assembly at the promoter and enhancer sites compromises Hand2 transcription, adversely affects fibroblast growth factor signaling pathways, prevents normal stromal-epithelial crosstalk, and disrupts embryo implantation. The mutant female mice are infertile and provide insight into potential causes of early pregnancy loss in humans.

Authors

Qiliang Xin, Iris Feng, Guoyun Yu, Jurrien Dean

×

Figure 1

Implantation failure and female infertility after uterine-specific Pbrm1 deletion.

Options: View larger image (or click on image) Download as PowerPoint
Implantation failure and female infertility after uterine-specific Pbrm1...
(A) Immunohistochemical staining showing the spatiotemporal expression of PBRM1 in WT uteri on D1, D4, and D5 of pregnancy. Bl, blastocyst; S, stromal. Scale bar: 100 mm. (B) RT-qPCR analysis of Pbrm1 mRNA levels in D4 uteri from Pbrm1fl/fl and Pbrm1cKO mice. Values are normalized to Gapdh expression and represented as mean ± SEM (n = 3). ***P < 0.001, independent-sample Student’s t test. (C) Immunoblotting of PBRM1 protein in D4 Pbrm1fl/fl and Pbrm1cKO uteri. β-actin, load control. (D) Immunohistochemistry of PBRM1 protein in D4 Pbrm1fl/fl and Pbrm1cKO uteri. Scale bar: 100 mm. (E) Number of ovulated eggs in Pbrm1fl/fl and Pbrm1cKO mice. Numbers within the bars indicate numbers of mice tested. (F) Average litter sizes of Pbrm1fl/fl and Pbrm1cKO female mice. Numbers within the bars indicate numbers of mice tested. Data are represented as mean ± SEM. ***P < 0.001, independent-sample Student’s t test. (G) Representative images of normal embryo morphology from D5 to D6 pregnant Pbrm1cKO mice, exhibiting embryo implantation failure in the uteri beyond D5. Scale bars: 1 cm (uterus); 100 mm (embryos).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts