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多囊卵巢综合征(polycystic ovary syndrome, PCOS)是临床中较常见的一种内分泌疾病,影响育龄期妇女的身体和心理健康。PCOS在临床表现方面异质性明显,主要以月经失调、不孕、高雄激素血症、卵巢多囊样改变为特征,常伴有糖脂代谢的异常,如肥胖和胰岛素抵抗等[1]。PCOS病人不孕的原因主要是排卵障碍、卵子质量差等[2],应用促排卵药物后,排卵率可高达90%[3]。然而,PCOS病人接受胚胎移植后流产率较高[4],这可能与PCOS病人子宫内膜容受性降低有关。有学者[5]通过蛋白组学研究发现,PCOS病人子宫内膜基因的差异性表达与其子宫内膜容受性差密切相关,进而可能直接影响PCOS病人的生育能力。子宫内膜容受性是影响胚胎种植成功与否的重要因素之一,因此,探讨PCOS病人于胚胎种植窗口期的子宫内膜容受性是否改变具有重要临床意义。基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-2(MMP-2)及组织金属蛋白酶抑制物-1(TIMP-1)在不同时期的子宫内膜中的表达具有差异性,这可能与子宫内膜功能相关。本研究通过检测MMP-9、MMP-2及TIMP-1在PCOS病人促排卵后种植窗口期的表达情况,探讨PCOS病人子宫内膜容受性的变化。现作报道。
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MMP-2、MMP-9、TIMP-1在对照组及PCOS组的内膜组织中均呈阳性表达,在间质细胞和腺上皮细胞的细胞质内均有棕黄色颗粒沉着,以腺上皮的表达为主(见图 1)。PCOS组子宫内膜腺上皮MMP-2、MMP-9及TIMP-1表达均明显低于对照组(P < 0.01),子宫内膜间质MMP-9表达亦低于对照组(P < 0.05)(见表 1)。
分组 n MMP-2 MMP-9 TIMP-1 腺上皮 PCOS组 12 0.221±0.012 0.237±0.012 0.247±0.018 对照组 15 0.251±0.033 0.278±0.015 0.301±0.023 t — 2.99 7.69 6.66 P — < 0.01 < 0.01 < 0.01 间质 PCOS组 12 0.102±0.015 0.092±0.015 0.099±0.021 对照组 15 0.095±0.032 0.107±0.017 0.105±0.012 t — 0.70 2.40 0.93 P — >0.05 < 0.05 >0.05 表 1 2组病人子宫内膜MMP-2、MMP-9及TIMP-1表达比较(x±s)
MMP-2、MMP-9及TIMP-1在多囊卵巢综合征病人种植窗口期内膜的表达及其临床意义
Expression of MMP-2、MMP-9 and TIMP-1 in endometrium of PCOS patients during the implantation window phase and its clinical significance
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摘要:
目的 检测基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-2(MMP-2)及组织金属蛋白酶抑制物-1(TIMP-1)在多囊卵巢综合征(PCOS)病人种植窗口期子宫内膜组织中的表达情况,并探讨其临床意义。 方法 选择接受促排卵后治疗的PCOS病人(PCOS组)12例和因男方因素不孕且月经正常前来就诊病人(对照组)15例,检测2组排卵后第7天子宫内膜组织中MMP-9、MMP-2和TIMP-1蛋白表达情况,利用病理图像分析技术,对实验结果进行半定量分析。 结果 MMP-9、MMP-2和TIMP-1在2组子宫内膜组织中均呈阳性表达,在间质细胞和腺上皮细胞的细胞质内均有棕黄色颗粒物沉着,以腺上皮表达为主。PCOS组子宫内膜腺上皮MMP-2、MMP-9及TIMP-1表达均明显低于对照组(P < 0.01),子宫内膜间质MMP-9表达亦低于对照组(P < 0.05)。 结论 MMP-9、MMP-2和TIMP-1在PCOS组病人的种植窗口期子宫内膜中的表达水平较低,这可能是导致PCOS病人采用促排卵治疗后妊娠率低、流产率高的原因之一。 -
关键词:
- 多囊卵巢综合征 /
- 子宫内膜 /
- 基质金属蛋白酶-2 /
- 基质金属蛋白酶-9 /
- 组织金属蛋白酶抑制物-1
Abstract:Objective To investigate the expression of matrix metalloproteinase(MMP)-9, MMP-2 and matrix metalloproteinase inhibitor-1(TIMP-1) in endometrium of polycystic ovary syndrome(PCOS) patients during the implantation window phase, and to explore its significance. Methods A total of 12 patients with PCOS who received post ovulation induction treatment(PCOS group) and 15 patients with infertility due to male factors and normal menstruation(control group) were selected.The expressions of MMP-9, MMP-2 and TIMP-1 proteins in endometrial tissue of the two groups on the seventh day after ovulation were detected.The pathology image analysis technology was employed to conduct the semi-quantitative analysis. Results The expressions of MMP-9, MMP-2 and TIMP-1 in the two groups in endometrium were positive, and the brown granule cell pigmentation was found in the glandular epithelial cells and stromal cells cytoplasm, especially in the former ones.The expressions of MMP-2, MMP-9 and TIMP-1 in endometrial glandular epithelium in PCOS group were significantly lower than those in control group(P < 0.01), and the expression of MMP-9 in endometrial stroma was also lower than that in control group(P < 0.05). Conclusions The low expression of MMP-9, MMP-2 and TIMP-1 in the implantation window phase of endometrium may be one of the causes of low pregnancy and high abortion rate in PCOS patients undergoing ovulation induction treatment. -
表 1 2组病人子宫内膜MMP-2、MMP-9及TIMP-1表达比较(x±s)
分组 n MMP-2 MMP-9 TIMP-1 腺上皮 PCOS组 12 0.221±0.012 0.237±0.012 0.247±0.018 对照组 15 0.251±0.033 0.278±0.015 0.301±0.023 t — 2.99 7.69 6.66 P — < 0.01 < 0.01 < 0.01 间质 PCOS组 12 0.102±0.015 0.092±0.015 0.099±0.021 对照组 15 0.095±0.032 0.107±0.017 0.105±0.012 t — 0.70 2.40 0.93 P — >0.05 < 0.05 >0.05 -
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