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

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

Source: Human Reproduction, Volume 22, Number 10, 24 October 2007 , pp. 2615-2622(8)

Publisher: Oxford University Press

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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.

Keywords: glycodelin; histone deacetylase inhibitor; implantation; SAHA

Document Type: Research article

DOI: http://dx.doi.org/10.1093/humrep/dem263

Publication date: 2007-10-24

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Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.

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

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