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- Title
Histone deacetylase inhibitor-induced glycodelin enhances the initial step of implantation.
- Authors
Hiroshi Uchida; Tetsuo Maruyama; Kuniaki Ohta; Masanori Ono; Toru Arase; Maki Kagami; Hideyuki Oda; Takashi Kajitani; Hironori Asada; Yasunori Yoshimura
- 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.
- Subjects
CELL culture; HISTONE deacetylase; AMIDASES; DIETHYLAMINE
- Publication
Human Reproduction, 2007, Vol 22, Issue 10, p2615
- ISSN
0268-1161
- Publication type
Article
- DOI
10.1093/humrep/dem263