Down-regulation of transcription factor OVOL2 contributes to epithelial-mesenchymal transition in a noninvasive type of trophoblast implantation to the maternal endometrium

Rulan Bai, Kazuya Kusama, Keigo Nakamura, Toshihiro Sakurai, Koji Kimura, Atsushi Ideta, Yoshito Aoyagi, Kazuhiko Imakawa

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5 Citations (Scopus)


Embryo implantation into the uterine endometrium is required for pregnancy establishment in most mammals. By using global expression analysis, we investigated the molecules that are related to epithelial- mesenchymal transition (EMT) in noninvasive bovine trophoblasts and found that the transcription factor, ovo-like zinc finger 2 (OVOL2), which is essential for mesenchymal-epithelial transition in various cancers, was downregulated after trophoblast attachment to the endometrial epitheliumin utero. In cultured bovine trophoblast cells, OVOL2 down-regulation occurred onlywhen cells were allowed to attach to bovine endometrial epithelial cells via the TEAD3/YAP signaling pathway. This resulted in the up-regulation of the EMT-associated transcription factors, ZEB1 and SNAI2, and the mesenchymal cell markers, N-cadherin (CDH2) and vimentin (VIM), whereas epithelial cellmarker, E-cadherin (CDH1), was down-regulated. In contrast, OVOL2 overexpression in bovine trophoblast cells exhibited a decrease in ZEB1 transcripts and an increase in E-cadherin. These observations revealed that ovo-like protein (OVOL)2 down-regulation occurred concurrently with conceptus implantation into the uterine endometriumvia theYAP/TEAD3 signaling pathway, and suggest that the down-regulation ofOVOL2 expression contributes to the up-regulation of EMT-related transcription factor expression,which enablesEMTprogression in the noninvasive bovine trophectoderm postimplantation.

Original languageEnglish
Pages (from-to)3371-3384
Number of pages14
JournalFASEB Journal
Issue number6
Publication statusPublished - Jun 1 2018



  • Bovine
  • TEAD
  • YAP

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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