Studies using an in vitro model show evidence of involvement of epithelial-mesenchymal transition of human endometrial epithelial cells in human embryo implantation

Hiroshi Uchida, Tetsuo Maruyama, Sayaka Uchida, Hideyuki Oda, Kaoru Miyazaki, Akiko Yamasaki, Yasunori Yoshimura

Research output: Contribution to journalArticle

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Abstract

Human embryo implantation is a critical multistep process consisting of embryo apposition/adhesion, followed by penetration and invasion. Through embryo penetration, the endometrial epithelial cell barrier is disrupted and remodeled by an unknown mechanism. We have previously developed an in vitro model for human embryo implantation employing the human choriocarcinoma cell line JAR and the human endometrial adenocarcinoma cell line Ishikawa. Using this model we have shown that stimulation with ovarian steroid hormones (17β-estradiol and progesterone, E2P4) and suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, enhances the attachment and adhesion of JAR spheroids to Ishikawa. In the present study we showed that the attachment and adhesion of JAR spheroids and treatment with E2P4 or SAHA individually induce the epithelial-mesenchymal transition (EMT) in Ishikawa cells. This was evident by up-regulation of N-cadherin and vimentin, a mesenchymal cell marker, and concomitant down-regulation of E-cadherin in Ishikawa cells. Stimulation with E2P4 or SAHA accelerated Ishikawa cell motility, increased JAR spheroid outgrowth, and enhanced the unique redistribution of N-cadherin, which was most prominent in proximity to the adhered spheroids. Moreover, an N-cadherin functional blocking antibody attenuated all events but not JAR spheroid adhesion. These results collectively provide evidence suggesting that E2P4- and implanting embryo-induced EMT of endometrial epithelial cells may play a pivotal role in the subsequent processes of human embryo implantation with functional control of N-cadherin.

Original languageEnglish
Pages (from-to)4441-4450
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number7
DOIs
Publication statusPublished - 2012 Feb 10

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Epithelial-Mesenchymal Transition
Cadherins
Epithelial Cells
Adhesion
Embryonic Structures
Steroid hormones
Cells
Cell Line
Choriocarcinoma
Histone Deacetylase Inhibitors
Blocking Antibodies
Ovulation Induction
Vimentin
Cell Movement
Progesterone
Estradiol
Adenocarcinoma
Up-Regulation
Down-Regulation
Steroids

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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Studies using an in vitro model show evidence of involvement of epithelial-mesenchymal transition of human endometrial epithelial cells in human embryo implantation. / Uchida, Hiroshi; Maruyama, Tetsuo; Uchida, Sayaka; Oda, Hideyuki; Miyazaki, Kaoru; Yamasaki, Akiko; Yoshimura, Yasunori.

In: Journal of Biological Chemistry, Vol. 287, No. 7, 10.02.2012, p. 4441-4450.

Research output: Contribution to journalArticle

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