Section of Endocrinology and Reproduction, Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, 4th Floor, Jessop Wing, Tree Root Walk, Sheffield S10 2SF, UK.
Reprod Biol Endocrinol. 2010 Jun 16;8:62. doi: 10.1186/1477-7827-8-62.
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.
我们最近发现，有反复妊娠丢失（RPL）病史的女性血清松弛素-2 水平降低。我们试图确定 RPL 病史是否也与血清基质金属蛋白酶（MMPs）和基质金属蛋白酶抑制剂（TIMP）-1 和 -2 的变化有关。
我们在妊娠 6-8、10-12、20 和 34 周时，从 20 名有 RPL 病史的孕妇和 20 名无 RPL 病史的年龄匹配孕妇（NRPL）以及脐带血中获得血清。我们通过 ELISA 定量测定总血清浓度 MMP-1、MMP-3、MMP-9 和 TIMP-1、TIMP-2。我们确定这些血清标志物水平是否与 RPL 病史和 37 周前分娩有关。
RPL 和 NRPL 之间的流产、早产或胎膜早破率没有差异。然而，RPL 出生的婴儿比 NRPL 出生的婴儿轻。RPL 和 NRPL 之间 MMP-1、9 和 TIMP-1 没有差异，但 6-8 周时 RPL 中的 MMP-3 更高（P<0.05）。所有孕期 RPL 妇女的血清 TIMP-2 水平均较高（P<0.01）。10-12 周时 RLX-2（之前报道过）与 TIMP-2 的比值与 RPL 病史的相关性强于两种肽单独的相关性 - RLX-2 的 ROC 曲线下面积为 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 比值为 0.92（95%CI 0.74 至 0.99）。
有 RPL 病史的妇女在随后的可行妊娠中表现出血清 TIMP-2 增加和 RLX-2 减少。在早期妊娠中测定这两种标志物可增强对有 RPL 病史的妇女的鉴别能力。这些观察结果表明，这两种肽在早期着床和胎盘发育中起作用。这些肽是否能成为指数妊娠中随后妊娠丢失的可靠早期预测标志物尚不清楚，需要进一步研究。
