Circulating levels of matrix proteases and their inhibitors in pregnant women with and without a history of recurrent pregnancy loss.

Circulating levels of matrix proteases and their inhibitors in pregnant women with and without a history of recurrent pregnancy loss.
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DOI:
10.1186/1477-7827-8-62
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发表时间:
2010-06-16
期刊:
Reproductive biology and endocrinology : RB&E
影响因子:
--
通讯作者:
Li TC
Li TC
中科院分区:
其他
文献类型:
--
作者:
Anumba DO;El Gelany S;Elliott SL;Li TC

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我们最近的研究表明,血清松弛素-2水平在有复发性流产史(RPL)的妇女中减弱。我们试图确定RPL病史是否也与血清基质金属蛋白酶(MMPs)和基质金属蛋白酶(TIMP) -1和-2的组织抑制剂的变化有关。我们从20名有RPL病史的孕妇和20名年龄匹配的无RPL病史的孕妇(妊娠6-8周、10-12周、20周和34周)和脐带血中提取血清。采用ELISA法定量测定血清中MMP-1、MMP-3、MMP-9、TIMP-1、TIMP-2的总浓度。我们确定这些血清标志物水平是否与妊娠37周前的RPL病史和分娩有关。RPL和NRPL在流产率、早产率和胎膜产前破裂率方面没有差异。然而,RPL出生的婴儿比NRPL出生的婴儿更轻。血清MMP-1、9和TIMP-1在RPL和NRPL之间无差异,但MMP-3在6-8周时RPL高于NRPL (P < 0.05)。RPL妇女各妊娠期血清TIMP-2水平均较高(P < 0.01)。RLX-2(先前报道)与TIMP-2的比值在妊娠10-12周与RPL病史的相关性比单独的任何一种肽更强——ROC曲线下面积RLX-2为0.79 (95% CI 0.57至0.92),TIMP-2为0.83 (95% CI 0.63至0.95),RLX-2:TIMP-2为0.92 (95% CI 0.74至0.99)。有RPL病史的妇女在随后的可存活妊娠期间表现出血清TIMP-2升高和RLX-2降低。在妊娠早期测定这两种标记物增强了对有RPL病史妇女的歧视。这些观察结果表明这两种肽在早期着床和胎盘发育中的作用。是否这些可能被证明是可靠的早期预测标志物在指数妊娠随后的妊娠丢失是未知的,将需要进一步的研究。
We have recently shown that serum relaxin-2 levels are attenuated in women with a history of recurrent pregnancy loss (RPL). We sought to determine whether a history of RPL is also associated with changes in serum matrix metalloproteases (MMPs) and tissue inhibitors of matrix metalloproteases (TIMP) -1 and -2. We obtained serum from 20 pregnant women with a history of RPL and 20 age-matched pregnant women with no history of RPL (NRPL) at 6-8, 10-12, 20, and 34 weeks gestation, and from cord blood. We quantified total serum concentrations of MMP-1, MMP-3, MMP-9 and TIMP-1 and TIMP-2 by ELISA. We determined whether these serum marker levels were associated with a history of RPL and delivery before 37 weeks gestation. There was no difference in the rates of miscarriage, preterm birth or prelabour rupture of fetal membranes between RPL and NRPL. However babies born to RPL were lighter than those born to NRPL. Serum MMP-1, 9, and TIMP-1 did not differ between RPL and NRPL but MMP-3 was higher in RPL vs. NRPL at 6-8 weeks (P < 0.05). Serum TIMP-2 levels were higher in RPL women at all gestations (P < 0.01). The ratio of RLX-2 (reported previously) to TIMP-2 at 10-12 weeks gestation was more strongly associated with a history of RPL than either peptide separately - area under the ROC curves for RLX-2 0.79 (95% CI 0.57 to 0.92), TIMP-2 0.83 (95% CI 0.63 to 0.95), and for RLX-2:TIMP-2 ratio 0.92 (95% CI 0.74 to 0.99). Women with a history of RPL demonstrate increased serum TIMP-2 and reduced RLX-2 during a subsequent viable pregnancy. Determination of both markers in early pregnancy enhances the discrimination of women with a history of RPL. These observations suggest roles for these two peptides in early implantation and placental development. Whether these may prove to be reliable early predictive markers for subsequent pregnancy loss in the index pregnancy is unknown and will require further studies.
DOI: 10.1016/j.ejogrb.2009.07.008
发表时间: 2009-11-01
影响因子: 2.6
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