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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 8

Expression of pSTAT3 in the physiological uterine regeneration process.

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Expression of pSTAT3 in the physiological uterine regeneration process.
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(A) Immunostaining of phosphorylated STAT3 (pSTAT3) in the nonpregnant and postpartum mouse uteri. As for the nonpregnant sample, a diestrus uterus was used. Immunoreactivity for pSTAT3 was observed in the luminal and glandular epithelium after delivery, in contrast to its negative staining in the nonpregnant uterus. (B) Immunostaining of pSTAT3 in the human uterus at the late secretory, menstrual, and early proliferative phases. Immunoreactivity for pSTAT3 was observed in the luminal and glandular epithelium at the menstrual and early proliferative phases, as opposed to the negative staining during the late secretory phase. l, luminal epithelium; g, glandular epithelium; s, stroma; m, myometrium. Each image is a representative from at least 3 independent experiments. Scale bar: 100 μm.

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