Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
STAT3 accelerates uterine epithelial regeneration in a mouse model of decellularized uterine matrix transplantation
Takehiro Hiraoka, … , Tomoyuki Fujii, Yutaka Osuga
Takehiro Hiraoka, … , Tomoyuki Fujii, Yutaka Osuga
Published June 2, 2016
Citation Information: JCI Insight. 2016;1(8):e87591. https://doi.org/10.1172/jci.insight.87591.
View: Text | PDF
Research Article Endocrinology Reproductive biology

STAT3 accelerates uterine epithelial regeneration in a mouse model of decellularized uterine matrix transplantation

  • Text
  • PDF
Abstract

Although a close connection between uterine regeneration and successful pregnancy in both humans and mice has been consistently observed, its molecular basis remains unclear. We here established a mouse model of decellularized uterine matrix (DUM) transplantation. Resected mouse uteri were processed with SDS to make DUMs without any intact cells. DUMs were transplanted into the mouse uteri with artificially induced defects, and all the uterine layers were recovered at the DUM transplantation sites within a month. In the regenerated uteri, normal hormone responsiveness in early pregnancy was observed, suggesting the regeneration of functional uteri. Uterine epithelial cells rapidly migrated and formed a normal uterine epithelial layer within a week, indicating a robust epithelial-regenerating capacity. Stromal and myometrial regeneration occurred following epithelial regeneration. In ovariectomized mice, uterine regeneration of the DUM transplantation was similarly observed, suggesting that ovarian hormones are not essential for this regeneration process. Importantly, the regenerating epithelium around the DUM demonstrated heightened STAT3 phosphorylation and cell proliferation, which was suppressed in uteri of Stat3 conditional knockout mice. These data suggest a key role of STAT3 in the initial step of the uterine regeneration process. The DUM transplantation model is a powerful tool for uterine regeneration research.

Authors

Takehiro Hiraoka, Yasushi Hirota, Tomoko Saito-Fujita, Mitsunori Matsuo, Mahiro Egashira, Leona Matsumoto, Hirofumi Haraguchi, Sudhansu K. Dey, Katsuko S. Furukawa, Tomoyuki Fujii, Yutaka Osuga

×

Figure 3

Regenerated uteri contribute to successful pregnancy.

Options: View larger image (or click on image) Download as PowerPoint
Regenerated uteri contribute to successful pregnancy.
(A) H&E staini...
(A) H&E staining and Ki67 immunostaining of the recipient mouse uteri on day 4 of pregnancy. Normal proliferation-differentiation switching during implantation, a marker of uterine receptivity, was observed in the transplanted decellularized uterine matrix (DUM), indicating the normal capacity for embryo implantation in the regenerated uterus. WT recipient mice 1 month after decellularized matrix transplantation were crossed with fertile WT males. Scale bar: 200 μm. UT, a recipient uterus surrounding DUM; dotted line, a boundary between DUM and UT. Each image is a representative from at least 3 independent experiments. (B) A macroscopic image of an implantation site at the transplanted DUM site on day 19 of pregnancy. To assess pregnancy outcome of WT recipient mice, cesarean section was performed on day 19 of pregnancy. The reconstructed uterus within the transplanted DUM site showed normal appearance and looked like a pregnant uterus on day 19. Yellow arrow, a 10-0 nylon suture thread. Scale bar: 2 mm. (C) Numbers of implantation sites in the surgical and nonsurgical horns in the pregnant recipient mice on day 19 of pregnancy. Numbers of implantation sites in the pregnant recipient mice were comparable between the surgical and nonsurgical horns. (D) A macroscopic image of pups in the surgical and nonsurgical horns of the same recipient mouse delivered by cesarean section on day 19 of pregnancy. Size and general appearance of pups at the transplanted DUM sites were similar to those of pups at the nonsurgical site as well as those of pups in the surgical horns. (E) Weight of pups that developed at the surgical site, the nonsurgical site in the surgical horn, and the nonsurgical horn on day 19 of pregnancy. The weight of pups that developed at the transplanted DUM sites were similar to those of pups that developed at the nonsurgical site as well as those of pups that developed in the surgical horns, indicating that regenerated uterine capacity was normal and could maintain full pregnancy.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts