Histone deacetylase inhibitor-induced glycodelin enhances the initial step of implantation.
Histone deacetylase inhibitor-induced glycodelin enhances the initial step of implantation.
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DOI：
10.1093/humrep/dem263
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发表时间：
2007-10
影响因子：
6.1
通讯作者：
H. Uchida;T. Maruyama;Kuniaki Ohta;M. Ono;T. Arase;M. Kagami;H. Oda;Takashi Kajitani;H. Asada;Y. Yoshimura
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文献类型：
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作者：
H. Uchida;T. Maruyama;Kuniaki Ohta;M. Ono;T. Arase;M. Kagami;H. Oda;Takashi Kajitani;H. Asada;Y. Yoshimura
背景：控制植入的复杂分子途径尚不清楚，伦理限制限制了人类研究。可逆组蛋白乙酰化调节基因转录，组蛋白去乙酰化酶抑制剂（HDACI）诱导特定基因。辛二酰苯胺异羟肟酸（SAHA）是一种新近被批准作为抗癌药物的HDACI，其通过上调分泌期优势蛋白glycodelin诱导人子宫内膜腺细胞的形态和功能分化。方法：我们使用人子宫内膜腺癌细胞系石川和绒毛膜癌细胞系K562，在体外植入试验中研究SAHA是否改善植入。结果在体外植入实验中，类胡萝卜素球状体与石川细胞的粘附呈时间依赖性。用卵巢类固醇激素或SAHA治疗后，Glycodelin诱导可增强着床。当glycodelin在没有刺激的情况下过表达并且几乎完全被glycodelin基因沉默消除时，也获得了植入的改善。结论：本研究表明glycodelin是着床的关键调节蛋白，并提示SAHA可能有能力取代类固醇衍生物治疗不孕症。
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.