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首页> 外文期刊>Molecular Human Reproduction >Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantationn failure and endometriosis
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Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantationn failure and endometriosis

机译：可育和不育患者子宫内膜的蛋白质组学分析表明载脂蛋白A-I在胚胎着床失败和子宫内膜异位症中的作用

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Pregnancy is dependent upon the endometrium acquiring a receptive phenotype that facilitates apposition, adhesion and invasion of a developmentally competent embryo. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry of mid-secretory endometrial biopsies revealed a 28 kDa protein peak that discriminated highly between samples obtained from women with recurrent implantation failure and fertile controls. Subsequent tandem mass spectroscopy unambiguously identified this peak as apolipoprotein A-I (apoA-I), a potent anti-inflammatory molecule. Total endometrial apoA-I levels were, however, comparable between the study and control group. Moreover, endometrial apoA-I mRNA expression was not cycle-dependent although there was partial loss of apoA-I immunoreactivity in luminal and glandular epithelium in mid-secretory compared with proliferative endometrial samples. Because of its putative anti-implantation properties, we examined whether endometrial apoA-I expression is regulated by embryonic signals. Human chorionic gonadotrophin (hCG) strongly inhibited apoA-I expression in differentiating explant cultures but not when established from eutopic endometrium from patients with endometriosis. Pelvic endometriosis was associated with elevated apoA-I mRNA levels, increased secretion by differentiating eutopic endometrial explant cultures and lack of hCG-dependent down-regulation. To corroborate these observations, we examined endometrial apoA-I expression and its regulation by hCG in a non-human primate model of endometriosis. As in humans, hCG strongly inhibited endometrial apoA-I mRNA expression in disease-free baboons, but this response was entirely lost upon induction of pelvic endometriosis. Together, these observations indicate that perturbations in endometrial apoA-I expression, modification or regulation by paracrine embryonic signals play a major role in implantation failure and infertility.
机译：怀孕取决于子宫内膜获得的受体表型，该表型有助于发育能力强的胚胎的并置，粘附和侵袭。分泌型子宫内膜活检的表面增强激光解吸/电离飞行时间质谱分析显示，28 kDa的蛋白峰与反复植入失败的女性样品和可育的对照样品之间存在高度差异。随后的串联质谱法明确地将该峰鉴定为载脂蛋白A-I（apoA-I），这是一种有效的抗炎分子。但是，研究组与对照组的子宫内膜apoA-I总水平相当。此外，尽管与增生性子宫内膜样品相比，分泌中段的腔和腺上皮中的apoA-I免疫反应性部分丧失，但子宫内膜apoA-I mRNA的表达不是周期依赖性的。由于其假定的抗植入特性，我们检查了子宫内膜apoA-I表达是否受胚胎信号调控。人绒毛膜促性腺激素（hCG）在分化的外植体培养物中强烈抑制apoA-I的表达，但是当从子宫内膜异位症患者的异位内膜中建立时，则不能。盆腔子宫内膜异位症与升高的apoA-I mRNA水平，通过区分异位子宫内膜外植体培养物的分泌增加和缺乏hCG依赖性下调有关。为了证实这些观察结果，我们检查了子宫内膜异位的非人类灵长类动物模型中子宫内膜apoA-I的表达及其对hCG的调控。与人类一样，hCG在无病的狒狒中强烈抑制子宫内膜apoA-I mRNA表达，但这种反应在盆腔子宫内膜异位症诱导后完全消失。总之，这些观察结果表明，旁分泌胚胎信号对子宫内膜apoA-I表达，修饰或调控的干扰在植入失败和不育中起主要作用。

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  • 来源
    《Molecular Human Reproduction》 |2010年第4期|p.273-285|共13页
  • 作者

    Asgerally T. Fazleabas;

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    Imperial College London, St Mary's Campus, @%@, The Rosie Hospital, University of Cambridge, @%@, Saitama Medical School, @%@, University of North Carolina at Chapel Hill, @%@, Greenville Hospital System, @%@, de Duve Institute, Universite catholique de;

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