Differential roles of uterine epithelial and stromal STAT3 coordinate uterine receptivity and embryo attachment

Takehiro Hiraoka, Yasushi Hirota, Yamato Fukui, Mona Gebril, Tetsuaki Kaku, Shizu Aikawa, Tomoyuki Hirata, Shun Akaeda, Mitsunori Matsuo, Hirofumi Haraguchi, Mayuko Saito-Kanatani, Ryoko Shimizu-Hirota, Norihiko Takeda, Osamu Yoshino, Tomoyuki Fujii, Yutaka Osuga

研究成果: Article査読

抄録

Although it has been reported that uterine signal transducer and activator of transcription 3 (STAT3) is essential for embryo implantation, the exact roles of uterine epithelial and stromal STAT3 on embryo implantation have not been elucidated. To address this issue, we generated Stat3-floxed/Ltf-iCre (Stat3-eKO), Stat3-floxed/Amhr2-Cre (Stat3-sKO), and Stat3-floxed/Pgr-Cre (Stat3-uKO) mice to delete Stat3 in uterine epithelium, uterine stroma, and whole uterine layers, respectively. We found that both epithelial and stromal STAT3 have critical roles in embryo attachment because all the Stat3-eKO and Stat3-sKO female mice were infertile due to implantation failure without any embryo attachment sites. Stat3-eKO uteri showed indented structure of uterine lumen, indicating the role of epithelial STAT3 in slit-like lumen formation in the peri-implantation uterus. Stat3-sKO uteri exhibited hyper-estrogenic responses and persistent cell proliferation of the epithelium in the peri-implantation uterus, suggesting the role of stromal STAT3 in uterine receptivity. In addition, Stat3-uKO female mice possessed not only the characteristic of persistent epithelial proliferation but also that of indented structure of uterine lumen. These findings indicate that epithelial STAT3 controls the formation of slit-like structure in uterine lumen and stromal STAT3 suppresses epithelial estrogenic responses and cell proliferation. Thus, epithelial and stromal STAT3 cooperatively controls uterine receptivity and embryo attachment through their different pathways.

本文言語English
論文番号15523
ジャーナルScientific reports
10
1
DOI
出版ステータスPublished - 2020 12 1

ASJC Scopus subject areas

  • General

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