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Study Of Mitogen-Activated Protein Kinases Of Murine Endometrium During Implantation Period

Posted on:2004-03-08Degree:MasterType:Thesis
Country:ChinaCandidate:D X CaoFull Text:PDF
GTID:2120360095457871Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Embryo implantation is the key period of reproduction, which includes blastocyst recognition, apposition, attachment, local extracelluar matrix (ECM) hydrolysis and embryo invasion. Successful implantation involves two-way complex molecular interactions between the trophectoderm epithelium of the mature blastocyst and luminal epithelium of the uterus and consists of a series of steps leading to an effective reciprocal signaling between the blastocyst and the uterus. These interactions are primarily dependent upon the coordinated actions of ovarian progesterone and estrogen, moreover, many other factors, such as growth factors, cytokines, ECM, adhension molecules, oligosaccharides and proteases, regarded as local mediators, endometrium and embryo have also expressed some specific receptors, via intracellular signal transduction chains and express some key genes, making receptivity of the uterus and synchronized development of the embryo to the blastocyst stage.Mitogen-activated protein kinases (MAPKs), which are activated by many different signal molecules, belong to a large family of serine/threonine protein kinases. There are three well-characterized subfamilies of MAPKs, and mainly include the extracellular signal-regulated kinases, p42 ERK1 and p44 ERK2, which lie in the intercrossing of intracellular signal pathways. They deliver extracellular signals from activated receptors to various cellular compartments, notably the nucleus, where they direct the execution of appropriate genetic programs, as a mediator of many growth factors, mitogens, cytokines, hormones or environmental stresses, involved in regulating gene expression, cell growth, proliferation, differentiation, apoptosis and many cellular events, controling a vast array of physiological processes. Numerous factors involved in implantation, for instance LIF, EGF, HB-EGF, IL, PG and Integrin , whose signal trnasduction have a direct relation with MAPK. Most of MAPK upstream molecules arethe molecular marker of the receptivity of endometrium during implantation period, for instance, evidence suggests EGF and its receptor EGFR may play a role in rendering the endometrium receptive to embryo implantation. The temporal and spatial expression of LeY oligosaccharide in the uterus suggests that this factor may be involved in cell-cell communication between the uterus and blastocyst during implantation period. It has some extent effect on other factors expression.However, there are limitied documents about receptor signal transduction within uterine endometrium during implantation. The factors regulating endometrial receptivity remain poorly understood. The objective of this dessert is to investigate MAPK's expression and location in differnt days of pregnancy, as more important, we try to elucidate the relation of MAPK and the receptivity of endometrium. Samples were taken from nonpregnant, pregnant and cultured endometrium cell, with using immunohistochemical staining, Western-blot methods. To better understand this interaction, we further characterized the expression patterns of EGFR messenger RNAs in the mouse uterus on days 1 to 8 of pregnancy.In the present study, we found: two isofonns of non-phospho MAPK was generally equally expressed in the nonpregnant and pregnant mice endometrium, and little difference among them. By contrast, phospho-MAPK was observed in luminal and glandular epithelial cells on day 2, 3, 4 of gestation. Especially, at the site of implantation of day 5,6, uterine stroma cell apposing the preimplantation blastocyst changed into the decidual cells and displayed a distinct immunostaining of phospho MAPK. Western-blot results showed p44 express stronger than p42 did, with both their peak expression were observed on day 5, during the period of uterine decidualization. RT PCR showed EGFR and EGF gene activity were upregulated at the time of blastocyst invasion and adhension, though this upregulation was not directly reflected in an increase in bioactivity EGF receptor. At meanwhile, the research of cultured endometrium c...
Keywords/Search Tags:implantation, endometrium, signal transduction, MAPK, EGFR, Le~Y, oligosaccharide
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