Histone deacetylase inhibitor-induced glycodelin enhances the initial step of implantation

Hiroshi Uchida, Tetsuo Maruyama, Kuniaki Ohta, Masanori Ono, Toru Arase, Maki Kagami, Hideyuki Oda, Takashi Kajitani, Hironori Asada, Yasunori Yoshimura

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46 Citations (Scopus)

Abstract

Background: The complex molecular pathways governing implantation are unclear and ethical limitations limit studies in humans. Reversible histone acetylation regulates gene transcription and histone deacetylase inhibitors (HDACI) induce specific genes. Suberoylanilide hydroxamic acid (SAHA), a HDACI recently approved as an anti-cancer drug, induces the morphological and functional differentiation of human endometrial gland cells through up-regulation of glycodelin, a secretory phase dominant protein. Methods: We investigated whether SAHA improves implantation in an in vitro implantation assay using the human endometrial adenocarcinoma cell line, Ishikawa and the choriocarcinoma cell line, JAR. Results: In an in vitro implantation assay, JAR spheroids attached and adhered to Ishikawa cells in a time dependent manner. Glycodelin induction, following treatment with ovarian steroid hormones or SAHA, enhanced implantation. The improvement in implantation was also obtained when glycodelin was overexpressed without stimulation and was almost completely abrogated by glycodelin gene silencing. Conclusions: This study demonstrates that glycodelin is a key regulatory protein of implantation and suggests that SAHA may have a capacity to supplant steroid derivatives in the treatment of infertility.

Original languageEnglish
Pages (from-to)2615-2622
Number of pages8
JournalHuman Reproduction
Volume22
Issue number10
DOIs
Publication statusPublished - 2007 Oct

Keywords

  • Glycodelin
  • Histone deacetylase inhibitor
  • Implantation
  • SAHA

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynaecology

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    Uchida, H., Maruyama, T., Ohta, K., Ono, M., Arase, T., Kagami, M., Oda, H., Kajitani, T., Asada, H., & Yoshimura, Y. (2007). Histone deacetylase inhibitor-induced glycodelin enhances the initial step of implantation. Human Reproduction, 22(10), 2615-2622. https://doi.org/10.1093/humrep/dem263