Font Size: a A A

The Expression And Regulation Of Activin A And Matrix Metalloproteinasas In Human Cytotrophoblast Cells

Posted on:2005-09-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:L ZhaoFull Text:PDF
GTID:1104360122490983Subject:Gynecology
Abstract/Summary:PDF Full Text Request
The bulk of the human placenta consists of branching chorionic villi with an outer syncytiotrophoblast, underlying cytotrophoblasts, and a stromal core. These villi float within the intervillous space that is filled with maternal blood, providing the primary surface area for nutrient and gas transport to the developing fetus. Other structures, called anchoring villi, are attached to the uterine wall by virtue of cytotrophoblast cell columns that contain several cell types that represent the stepwise transition from basement membrane - associated, villous cytotrophoblast cells to invasive extravillous cytotrophoblast cells that migrate into the decidua and invade the maternal arterioles of the myometrium. Normal development of the placenta depends on the orchestrated balance of cytotrophoblast cell proliferation and differentiation into either one of the differentiated cell types, syncytiotrophoblast or invasive cytotrophoblasts. Abnormalities in these processes may lead to gestational abnormalities such as miscarriage, fetal growth restriction, and preeclampsia. Preeclampsia is an interesting disease of pregnancy in which there is an excess of cytotrophoblast cell proliferation as well as an interruption in the progression from villous to invasive extravillous cytotrophoblast cells.The stepwise progression starting from villous cytotrophoblasts, to transitional extravillous cytotrophoblast in the column, finally to invasive extravillous cytotrophoblast are complex processes that are temporally and spatially restricted, and coordinately regulated by various factors derived both embryo and maternal uterus. During the processes, the controlled invasion of trophoblast intothe maternal endometrium is one of the critical events that involves the degradation and remodeling of extracellular matrix ( ECM) as well as the modification of the uterine vessels. Matrix metalloproteinasa (MMPs) are main proteinases to degrade the ECM during implantation. The activities of MMPs are physiologically inhibited by their tissue inhibitors (TIMPs). Activin A is dimeric glycopro-tein belonging to the transforming growth factors |3 family. Activin A is a local regulator of human cytotrophoblast ceE differentiation and production of MMPs. In early and mid pregnancy, maternal serum activin A levels are stable and low, rising dramatically from approximately 24 weeks of gestation, reaching peak levels proximate to term. The feto - placental unit and fetal membrance are the main source of circulating activin A. However, owing to the limited availability of specimens, much information about MMPs, TIMPS, avtivin A has yet to be unclear concerning to the fetal ?maternal cross - talk, especially at the very early stage of human embryo implantation. Thus it is necessary to establish the suitable research model. Tubal pregnancy is a kind of abnormal gestation. It was reported that the behavior of trophoblast during the process might be similar to that in normal pregnancy. Furthermore, it is even possible to obtain samples containing intact maternal -fetal interface as early as the 3rd week of gestation.The objectives of our current study were to determine (1) The spatial and temporal expression of MMP - 2, - 9, - 26 and TIMP - 1, - 2, - 3 at the maternal - fetal interface of tubal implantation during week 3 to 9 of gestations and human normal pregnancy by immunohistichemistry and in sute hybridization at early stage. (2) The effects of activin A on the expression of matrix metallo-protainasa - 2, - 9, - 26 in cultured human cytotrophoblast cells during the first trimester. (3 ) The relationship between activin A, follistatin and pre-eclampsia.The results showed that the expression of various MMPs and TIMPs at the maternal - fetal interface of tubal pregnancy was very similar to those in normal uterine pregnancy. And during different periods of implantation, the invasion of extravillous cytotrophoblast cells ( EVCT) were precisely controlled by the co -ordinated expression of MMPs and TIMPs. During first trimester, EVCT exhibits...
Keywords/Search Tags:activin A, matrix metalloproteinase, cytotrophoblast, preeclampsia
PDF Full Text Request
Related items