Histone deacetylase inhibitor-induced glycodelin enhances the initial step of implantation.
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.
Uchida
Hiroshi
H
Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
Maruyama
Tetsuo
T
Ohta
Kuniaki
K
Ono
Masanori
M
Arase
Toru
T
Kagami
Maki
M
Oda
Hideyuki
H
Kajitani
Takashi
T
Asada
Hironori
H
Yoshimura
Yasunori
Y
D045744:Cell Line, Tumor; D010064:Embryo Implantation / Q000187:drug effects*; D020868:Gene Silencing; D000071816:Glycodelin; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D011257:Pregnancy Proteins / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation; D000077337:Vorinostat
D000071816:Glycodelin; D006023:Glycoproteins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D000077337:Vorinostat