The contribution of leukemia inhibitory factor (LIF) for embryo implantation differs among strains of mice
The contribution of leukemia inhibitory factor (LIF) for embryo implantation differs among strains of mice
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DOI：
10.1016/j.imbio.2014.03.011
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发表时间：
2014-07-01
期刊：
影响因子：
2.8
通讯作者：
Hondo, Eiichi
中科院分区：
文献类型：
--
作者：
Kobayashi, Ryosuke;Terakawa, Jumpei;Hondo, Eiichi
尽管声称母体白血病抑制因子 (LIF)（细胞因子白细胞介素 6 (IL6) 家族的成员）在小鼠胚胎植入中发挥着不可或缺的作用，但这些作用在人类中仍然不确定，因为 LIF 对植入的效力似乎因个体而异。在这里，我们表明 LIF 对小鼠植入的贡献取决于小鼠品系（ICR、C57BL/6J (B6)、ddY、BALB/c、DBA/2Cr 和 MF1 品系）。在植入期间抑制 LIF 会导致 B6 和 MF1 品系的胚胎植入严重中断。其他品系的植入部分受到干扰，但一些胚胎成功植入。我们推测其他 IL6 家族成员补偿了 ICR、ddY、BALB/c 和 DBA/2Cr 菌株植入时 LIF 的作用。事实上，Ctf1 的表达水平因 LIP 功能的阻断而上调。 CT-1（由 Ctf1 编码）治疗通过子宫腔上皮中信号转导器和转录激活剂 3 (STAT3) 的磷酸化，在延迟着床小鼠（ICR 和 B6）中诱导成功着床，无需 LIF。同时抑制 LIP 和 CT-1 并没有完全阻止 ICR 小鼠的着床，表明该品系中的胚胎着床受到 LIP、CT-1 和其他潜在 STAT3 激活剂的强有力保护。本研究可能为人类胚胎植入 LIF 效力的个体差异提供解释。 (c) 2014 年爱思唯尔有限公司。版权所有。
Despite of the claim that maternal leukemia inhibitory factor (LIF) - a member of interleukin 6 (IL6) family of cytokines - plays indispensable roles for murine embryo implantation, these roles remain undefined in humans because the potency of LIF on implantation appears to vary among individuals. Here, we showed that the contribution of LIF for murine implantation was dependent on the strains of mice (ICR, C57BL/6J (B6), ddY, BALB/c, DBA/2Cr and MF1 strains). Inhibition of LIF during the implantation period caused severe disruption of embryo implantation in B6 and MF1 strains. Implantation was partly disrupted in other strains, but some embryos were implanted successfully. We speculated that other IL6 family members compensate for LIF actions on implantation in ICR, ddY, BALB/c, and DBA/2Cr strains. Indeed, the expression level of Ctf1 was upregulated by blockage of LIP function. CT-1 (encoded by Ctf1) treatment induced successful implantation without LIF in delayed implantation mice (ICR and B6) via phosphorylation of the signal transducer and activator of transcription 3 (STAT3) in the uterine luminal epithelium. Simultaneous inhibition of LIP and CT-1 did not block implantation completely in ICR mice, indicating that embryo implantation in this strain was robustly protected by LIP, CT-1 and other potential STAT3 activators. The present study might provide an explanation for the individual variation in the potency of LIF for embryo implantation in humans. (c) 2014 Elsevier GmbH. All rights reserved.