Regulation of HOXA-10 and its expression in normal and abnormal endometrium

Regulation of HOXA-10 and its expression in normal and abnormal endometrium
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DOI:
10.1093/molehr/5.9.866
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发表时间:
1999-09-01
影响因子:
4
通讯作者:
Lessey, BA
Lessey, BA
中科院分区:
医学2区
文献类型:
--
作者:
Gui, YT;Zhang, JN;Lessey, BA

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Hoxa-10是一个基因家族的成员,该基因在发育过程中充当转录因子,已被证明对子宫功能具有重要作用。免疫组织化学和核糖核酸酶保护分析(RPA)显示,HOXA-10在上皮细胞和基质细胞中均有表达,在种植窗期表达增强。体外培养分离的子宫内膜上皮或间质Hoxa-10,雌二醇(10(-8)m o l/L)或不加黄体酮(10(-6)m o l/L)处理后,Hoxa-10的表达均增加。在基质细胞中,雌二醇和孕酮均可增加Hoxa-10的表达,且呈相加作用。松弛素(30 ng/ml)可进一步增加间质Hoxa-10的表达。Hoxa-10在正常月经周期中的表达与子宫内膜异位症和可疑子宫容受性缺陷妇女的子宫内膜进行了比较。在子宫内膜异位症患者中,腔内、腺体或内皮细胞中Hoxa-10的表达几乎没有差异,但间质中Hoxa-10的表达显著减少。总之,HOXA-10是一种激素调节的子宫内膜转录因子,似乎对卵巢类固醇和松弛素都有反应。这种核蛋白在着床窗口的上皮和间质中的出现,可能为子宫容受性的调节提供新的见解,并有助于识别对成功妊娠至关重要的其他基因。
HOXA-10 is a member of a family of genes that serve as transcription factors during development and have been shown to be important for uterine function. Using immunohistochemistry and RNAse protection assays (RPA), HOXA-10 was shown to be expressed in both epithelial and stromal cells with increased expression during the window of implantation. By in-vitro culture of isolated endometrial epithelium or stroma, HOXA-10, expression was increased after treatment with oestradiol (10(-8) mol/l) with or without progesterone (10(-6) mol/l). In stromal cells, oestradiol and progesterone both appeared to increase HOXA-10 expression and were additive. Relaxin (30 ng/ml) appeared to further increase stromal HOXA-10 expression. HOXA-10 expression during the window of implantation was compared in normal menstrual cycles to endometrium from women with endometriosis and suspected defects in uterine receptivity. Little or no difference was seen in luminal, glandular or endothelial HOXA-10 expression but a significant reduction in stroma HOXA-10 expression was noted in women with endometriosis. In conclusion, HOXA-10 is a hormone-regulated endometrial transcription factor that appears to be responsive to both ovarian steroids and relaxin. The appearance of this nuclear protein during the window of implantation in epithelium and stroma may offer new insight into the regulation of uterine receptivity and assist in the identification of other genes that are critical to the establishment of a successful pregnancy.