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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.
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Research Article Endocrinology Reproductive biology

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

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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

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Figure 7

STAT3 modulates uterine epithelial regeneration.

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STAT3 modulates uterine epithelial regeneration.
(A) Immunostaining of p...
(A) Immunostaining of phosphorylated STAT3 (pSTAT3) in the ovariectomized mouse DMT model. Immunoreactivity for pSTAT3 was observed primarily in the epithelium of UT at DMT-6h and became more intense at DMT-24h. (B–D) Evaluation of epithelial regeneration comparing ΔStat3 and WT mice. (B) Negative staining of pSTAT3 in the ΔStat3 mouse uterus ensured efficient knockout of uterine Stat3. (B and C) The number of flat cells on the decellularized uterine matrix (DUM) that reconstitute the epithelium was significantly decreased in ΔStat3 mice (**P < 0.01), and (B and D) the percentage of Ki67-positive epithelial cells in the recipient uterus surrounding DUM was significantly lower in ΔStat3 mice than that in WT mice (**P < 0.01), suggesting the significant retardation of epithelial regeneration due to uterine deletion of Stat3 (ΔStat3). 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. Scale bar: 200 μm.

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

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