The effect of leukemia inhibitory factor (LIF) on trophoblast differentiation: A potential role in human implantation
The effect of leukemia inhibitory factor (LIF) on trophoblast differentiation: A potential role in human implantation
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DOI：
10.1210/jc.81.2.801
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发表时间：
1996-02-01
影响因子：
5.8
通讯作者：
Arici, A
中科院分区：
文献类型：
--
作者：
Nachtigall, MJ;Kliman, HJ;Arici, A
白血病抑制因子（LIF）是一种多功能糖蛋白，与小鼠的正常着床密切相关。我们最近确定LIF在人子宫内膜中以月经周期依赖性方式表达。在月经周期的第19天和第25天之间观察到最大表达，与人类植入的时间一致。在这项研究中，我们已经利用纯化的培养人细胞滋养层细胞研究LIF的滋养层分化的几个形态学和生化标志物的影响。我们从足月胎盘中纯化人细胞滋养层细胞，并在有和没有LIF（10 ng/mL）的情况下培养它们。在24、48、72和96 h测定人CG、癌胚纤维连接蛋白和孕酮的分泌。北方印迹分析用于评估β hCG和癌胚纤维连接蛋白的信使RNA（mRNA）表达。我们发现，LIF显着降低滋养层细胞的hCG蛋白的生产在72和96小时，以及β hCG mRNA的表达。LIF还显著增加癌胚纤维连接蛋白mRNA的表达和蛋白的分泌。LIF不影响培养的滋养层细胞的类固醇生成活性，孕酮的产生。这些生化变化是细胞滋养层向锚定绒毛外表型分化的特征。因此，LIF似乎是通过直接调节滋养层分化而成为人类胚胎着床的重要调节因子。
Leukemia inhibitory factor (LIF) is a multifunctional glycoprotein strongly associated with normal implantation in the mouse. We have recently determined that LIF is expressed in the human endometrium in a menstrual cycle dependent manner. Maximal expression is observed between days 19 and 25 of the menstrual cycle, coinciding with the time of human implantation. In this study we have utilized purified cultures of human cytotrophoblasts to examine the effects of LIF on several morphologic and biochemical markers of the trophoblastic differentiation. We purified human cytotrophoblasts from term placentae and cultured them with and without LIF (10 ng/mL). The secretion of human CG, oncofetal fibronectin, and progesterone were measured at 24, 48, 72, and 96 h. Northern blot analysis was used to assess messenger RNA (mRNA) expression of beta hCG and oncofetal fibronectin. We found that LIF markedly decreased trophoblast production of hCG protein at 72 and 96 h, as well as expression of beta hCG mRNA. LIF also significantly increased the expression of oncofetal fibronectin mRNA and secretion of the protein. LIF did not affect steroidogenic activity of cultured trophoblasts, as determined by progesterone production. These biochemical changes are characteristic of cytotrophoblast differentiation toward an anchoring extravillous phenotype. Thus, LIF appears to be an important regulator of human embryonic implantation by directly modulating trophoblast differentiation.