Endometrial cysteine-rich secretory protein 3 is inhibited by human chorionic gonadotrophin, and is increased in the decidua of tubal ectopic pregnancy
Endometrial cysteine-rich secretory protein 3 is inhibited by human chorionic gonadotrophin, and is increased in the decidua of tubal ectopic pregnancy
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DOI：
10.1093/molehr/gap019
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发表时间：
2009-05-01
影响因子：
4
通讯作者：
Critchley, H. O. D.
中科院分区：
文献类型：
--
作者：
Horne, A. W.;Duncan, W. C.;Critchley, H. O. D.
异位妊娠（EP）仍然是一个相当大的原因发病率和偶尔死亡。目前，没有可靠的测试来区分异位妊娠和宫内妊娠。我们以前使用阵列技术证明，异位妊娠和宫内妊娠妇女蜕膜化子宫内膜中基因表达的差异可用于鉴定EP的候选诊断生物标志物。本研究的目的是进一步研究在EP中具有最高倍数增加的蜕膜基因，富含半胱氨酸的分泌蛋白-3（CRISP-3）。对接受手术终止妊娠（n = 8）、流产子宫排空（n = 6）和EP手术（n = 11）的妊娠匹配妇女的蜕膜化子宫内膜进行定量RT-PCR、形态学评估、免疫组化和western blot分析。分析血清孕酮和人绒毛膜促性腺激素（hCG）水平。用生理浓度的hCG培养永生化子宫内膜上皮细胞。CRISP-3 mRNA和蛋白在异位妊娠子宫内膜中的表达均高于宫内妊娠子宫内膜（P < 0.05）。CRISP-3蛋白定位于子宫内膜上皮细胞和粒细胞。与宫内妊娠相比，异位妊娠妇女的CRISP-3血清浓度没有差异。CRISP-3在子宫内膜中的表达与蜕膜化程度或血清孕酮水平无关。子宫内膜CRISP-3表达与血清hCG浓度成反比（P < 0.001）。hCG体外刺激子宫内膜上皮细胞后，CRISP-3表达降低（P < 0.01）。CRISP-3在子宫内膜中的检测可为不明部位早孕失败的诊断提供额外的工具。在患有EP的女性的蜕膜化子宫内膜中CRISP-3表达没有局部减少可能是由于滋养层的异位位置导致hCG暴露减少。
Ectopic pregnancy (EP) remains a considerable cause of morbidity and occasional mortality. Currently, there is no reliable test to differentiate ectopic from intrauterine gestation. We have previously used array technology to demonstrate that differences in gene expression in decidualized endometrium from women with ectopic and intrauterine gestations could be used to identify candidate diagnostic biomarkers for EP. The aim of this study was to further investigate the decidual gene with the highest fold increase in EP, cysteine-rich secretory protein-3 (CRISP-3). Decidualized endometrium from gestation-matched women undergoing surgical termination of pregnancy (n = 8), evacuation of uterus for miscarriage (n = 6) and surgery for EP ( n 11) was subjected to quantitative RT-PCR, morphological assessment, immunohistochemistry and western blot analysis. Sera were analysed for progesterone and human chorionic gonadotrophin (hCG) levels. Immortalized endometrial epithelial cells were cultured with physiological concentrations of hCG. CRISP-3 mRNA and protein expression were greater in endometrium from ectopic when compared with intrauterine pregnancies (P < 0.05). CRISP-3 protein was localized to epithelium and granulocytes of endometrium. CRISP-3 serum concentrations were not different in women with ectopic compared with intrauterine pregnancies. CRISP-3 expression in endometrium was not related to the degree of decidualization or to serum progesterone levels. Endometrial CRISP-3 expression was inversely proportional to serum hCG concentrations (P < 0.001). Stimulation of endometrial epithelial cells with hCG in vitro caused a reduction in CRISP-3 expression (P < 0.01). The measurement of CRISP-3 in endometrium could provide an additional tool in the diagnosis of failing early pregnancy of unknown location. The absence of a local reduction in expression of CRISP-3 in decidualized endometrium of women with EP may be due to reduced exposure to hCG due to the ectopic location of the trophoblast.