Kisspeptins and the placenta:: Regulation of trophoblast invasion
Kisspeptins and the placenta:: Regulation of trophoblast invasion
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DOI：
10.1007/s11154-007-9030-8
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发表时间：
2007-03-01
影响因子：
8.2
通讯作者：
Desoye, Gernot
中科院分区：
文献类型：
--
作者：
Hiden, Ursula;Bilban, Martin;Desoye, Gernot
绒毛外滋养细胞侵入子宫壁对胎盘和胎儿发育至关重要，其失调与多种异常妊娠有关。从机制上讲，滋养层细胞的侵袭与肿瘤细胞的侵袭非常相似，但在时间和空间上有严格的调节。这种调节是由不同的因子完成的，包括细胞因子和激素，它们由胎儿和母体组织产生，即，胎盘和子宫。最近，KiSS-1基因的产物（kisspeptins）已被鉴定为不仅抑制各种肿瘤中的转移，而且通过与G蛋白偶联受体KiSS-1 R结合来抑制滋养层侵袭。在胎盘中，接吻肽及其受体的表达水平分别在人类妊娠前三个月和大鼠妊娠第12.5天最高。这与入侵高峰和入侵调节至关重要的时间相吻合。人类kisspeptin主要由合胞体滋养层产生，而KiSS-1 R在入侵的绒毛外滋养层上也表达，表明合胞体滋养层对绒毛外滋养层入侵的旁分泌调节。在结构上不同的大鼠胎盘KiSS-1及其受体主要表达的浸润性滋养层巨细胞，从而建立了自分泌系统在这个滋养层亚群的入侵调节。在所有kisspeptin中，高度保守的kisspeptin Kp-10具有最强的侵袭抑制作用，表明其在滋养层侵袭调节中的主要作用。
The invasion of extravillous trophoblasts into the uterine wall is of crucial importance for placental and fetal development, and its dysregulation has been implicated in a wide spectrum of abnormal pregnancies. Mechanistically, trophoblast invasion strongly resembles the invasion of tumour cells, but differs from it by tight regulation in time and space. This regulation is accomplished by different factors including cytokines and hormones, which are produced by both fetal as well as maternal tissues i.e., placenta and uterus, respectively. Recently, products of the KiSS-1 gene (kisspeptins) have been identified to not only inhibit metastasis in various tumours, but also to repress trophoblast invasion via binding to the G protein-coupled receptor KiSS-1R. In the placenta, expression levels of kisspeptins and their receptor are highest in the first trimester in humans and at day 12.5 in rats, respectively. This coincides with the time when invasiveness peaks and invasion regulation is of central importance. Human kisspeptins are predominantly produced by the syncytiotrophoblast, whereas KiSS-1R is additionally expressed on the invading extravillous trophoblasts indicating a paracrine regulation of extravillous trophoblast invasion by the syncytiotrophoblast. In the structurally different rat placenta both KiSS-1 and its receptor are predominantly expressed by the invasive trophoblast giant cells, thus establishing an autocrine system in the invasion regulation of this trophoblast subpopulation. Amongst all kisspeptins the highly conserved kisspeptin Kp-10 has strongest invasion inhibiting effects suggesting its major role in regulation of trophoblast invasion.