Dynamic expression of matrix metalloproteinases (MMP-2,-9 and-14) and the tissue inhibitors of MMPs (TIMP-1,-2 and-3) at the implantation site during tubal pregnancy
Dynamic expression of matrix metalloproteinases (MMP-2,-9 and-14) and the tissue inhibitors of MMPs (TIMP-1,-2 and-3) at the implantation site during tubal pregnancy
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DOI：
10.1530/rep.1.00283
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发表时间：
2005-01-01
期刊：
影响因子：
3.8
通讯作者：
Piao, YS
中科院分区：
文献类型：
--
作者：
Bai, SX;Wang, YL;Piao, YS
基质金属蛋白酶（Matrix metalloproteinases，MMPs）是细胞外基质（extracellular matrix，ECM）降解的主要酶，其功能受组织基质金属蛋白酶抑制剂（tissue inhibitor of MMPs，TIMPs）的调节。MMPs和TIMPs在人类着床和胎盘形成中的作用的证据仍然不足，特别是在早期阶段。输卵管妊娠与正常宫内妊娠有一些相似之处，因此可能为着床研究提供一个独特的模型。本研究应用免疫组织化学和原位杂交技术检测输卵管妊娠母胎界面MMP-2、MMP-9、MMP-14和TIMP-1、TIMP-2、TIMP-3的表达。MMP-9和TIMP-1、-2和-3在所有类型的绒毛外细胞滋养层（EVCT）细胞中均有表达，而MMP-2和-14主要存在于远端柱细胞滋养层（CCT）细胞和侵袭性EVCT细胞中。同时，MMP-14和TIMP-1和-2的强度在向母体子宫内膜的侵袭途径中沿着增加。此外，VCT细胞中MMP-2、MMP-9、MMP-14和TIMP-1、TIMP-2、TIMP-3均呈阳性表达。在妊娠3 ~ 9周，MMP-9、TIMP-1和TIMP-3的mRNA水平和免疫反应性均随妊娠进展而升高，而TIMP-2的mRNA水平和免疫反应性则随妊娠进展而降低。各种MMPs和TIMPs在胎儿-母体界面的独特表达模式表明，它们可能在着床和胎盘形成过程中调节滋养层细胞的受控侵入。同时，该研究为更好地理解人类妊娠期间，特别是植入起始阶段的细胞事件机制提供了帮助。
Matrix metalloproteinases (MMPs) are responsible for extracellular matrix (ECM) degradation, and their functions are regulated by tissue inhibitors of MMPs (TIMPs). The evidence for the roles of MMPs and TIMPs in implantation and placentation has remained insufficient in humans, especially during the early stages. Tubal pregnancy has some similarities to normal intrauterine pregnancy and therefore may provide a unique model for implantation studies. in the present study, the expression of MMP-2, -9 and -14, and TIMP-1, -2 and -3 at the feto-maternal interface during tubal pregnancy was examined by immunohistochemistry and in situ hybridization. We found that MMP-9 and TIMP-1, -2 and -3 are produced by all types of extravillous cytotrophoblast (EVCT) cells, while MMP-2 and -14 mainly exist in distal column cytotrophoblast (CCT) cells and invasive EVCT cells. Meanwhile, the intensity of MMP-14 and TIMP-1 and -2 increased along the invasive pathway toward maternal interstitium. In addition, MMP-2, -9 and -14 and TIMP-1, -2 and -3 were all detected in the villous CT (VCT) cells. Furthermore, both the mRNA level and immunoreactivity of MMP-9, TIMP-1 and -3 increased, while those of TIMP-2 decreased concurrent with the progression of pregnancy during weeks 3-9. The unique expression pattern of various MMPs and TIMPs at the feto-maternal interface suggests that they may have roles in regulating the controlled invasion of trophoblasts during implantation and placentation. Meanwhile, the study provides a better understanding of the mechanisms involved in cellular events during human pregnancy, especially at the initiation stage of implantation.