2011-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/659612摘要：滋養層母細胞的絨毛化(syncytialization)是否完全，影響胎盤的正常發育與否。甚至有些妊娠期病症與此亦息息相關，子宮內生長受限及子癇前症就是例子。從目前我們的研究資料顯示，MUC1 及MUC15 隨著懷孕週數的增加，表現量也愈來愈明顯。MUC15 在syncytiotrophoblast 的epical membrane 最明顯。我們最近的研究又發現severe preeclampsia 的villi，其MUC15 的基因表現量會降低，所以MUC15 應該是對於syncytiotrophoblast 有保護作用。所以我們設計了一個3 年期的計劃，依序研究(1)刺激BeWo cells syncytialization過程中MUC15 的角色，還有MUC15 overexpression 或knockdown 時，對於syncytiotrophoblast 的functioning 及表現phenotype 的影響。(2)一系列實驗以明瞭MUC15 overexpression 或knockdown 時之cell mechanism，以及對於syncytiotrophoblast的repair or cell cycles 的影響。。(3) Knockout mice 的animal model，可以in vivo 或exvivo，了解不同妊娠時期的變化，同時包括研究cellular signaling 的pathway。本研究可以通盤探討黏液蛋白MUC15 與子癇前症的致病機轉的關聯，黏液蛋白如何調控滋養層母細胞的行為以及找出更精緻的子癇前症的偵測方法或甚至治療方式，十分重要。本研究為前瞻性先驅實驗。<br> Abstract: The anatomical integrity of the syncytiotrophoblast is critical, as a variety of transporters,receptors and enzymes are strategically positioned on the maternal blood facing microvillousplasma membrane, the basal plasma membrane facing the villous core, or both to regulatematernal–fetal exchange.Whereas placental function is critical at all stages of pregnancy, nutrient transportdemands on chorioallantoic villi in general, and villous trophoblasts in particular, are highestas the fetus triples in weight during the third trimester of gestation. This said, apoptosis ofvillous trophoblasts increases as pregnancy progresses, and insults that yield villous injurymay not be accompanied by a compensatory increase in cytotrophoblast proliferation anddifferentiation. Therefore, imbalances of injury and repair and maldevelopment of the villoustree are characteristic of the placenta in IUGR.Our results demonstrated that MUC15 expression increased with gestational age of thehuman placenta. Immunohistochemistry revealed that mucins in placental villi was mainlyexpressed by syncytiotrophoblasts throughout pregnancy. Most of the MUC1 is located at theepical membranes of syncytiotrophoblasts. The crude results also showed that MUC15expression is lower in severe preeclampsia than normal pregnancy.Therefore we design a three year proposal to study the correlation between MUC15and IUGR and preeclampsia. The BeWo cells will be induced to syncytialization. Thefunctioning property and modulation of cell cycles will be studied by MUC15overexpression or SiRNA knockdown on the BeWo cells or other cells. The knockoutmice model is introduced into this study to fulfill more cellular manipulations.The proposed research is significant in that: (1) it will contribute to the understandingof preeclamptic changes of surface mucin-like glycoproteins; (2) it will provide theknowledge how the trophoblast phenotypes are affected and regulated by surface mucin-likeglycoproteins; and (3) the gained information will allow us, in future studies, to develop newdiagnostic and therapeutic reagents for severe preeclampsia.This is absolutely a pioneer study.