title: STAT3 accelerates uterine epithelial regeneration in a mouse model of decellularized uterine matrix transplantation.
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 ofStat3conditional 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.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Hiraoka
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Precursory Research for Innovative Medical Care (PRIME), Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hirota
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Saito-Fujita
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Matsuo
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Mahiro
authors.initials: M
authors.lastname: Egashira
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Leona
authors.initials: L
authors.lastname: Matsumoto
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Haraguchi
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Sudhansu K
authors.initials: SK
authors.lastname: Dey
authors.affiliation: Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan.
authors.forename: Katsuko S
authors.initials: KS
authors.lastname: Furukawa
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Osuga