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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 4

Early phase of uterine reconstruction process in DMT.

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Early phase of uterine reconstruction process in DMT.
(A) An early phase...
(A) An early phase of uterine reconstruction process in the transplanted decellularized uterine matrices (DUMs) was assessed by H&E staining. Flat cells rapidly migrated onto the DUM on day 1, and they increased in number and became taller on day 3. Luminal epithelium was fully reconstructed, and stromal regeneration with glandular structure was also observed by day 7. Yellow arrowheads, cells constituting regenerating epithelium on DUM. (B) Immunostaining of cytokeratin 8 (CK8), estrogen receptor α (ERα), and progesterone receptor (PR) in the transplanted DUM on day 1. Flat cells on DUM exhibited prominent immunoreactivity for these proteins. Yellow arrowheads, flat cells constituting the regenerating epithelium on DUM. (C) Fluorescence assay of the transplantation site in the R26GRR/Ltf-iCre recipient uterus on day 3. Regenerating epithelium expressed tdsRed, indicating that it was the progeny of neighboring epithelial cells in UT. UT, a recipient uterus surrounding DUM; l, luminal epithelium; g, glandular epithelium; s, stroma; yellow arrowheads, cells constituting regenerating epithelium on 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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