Cai L Q, Cao Y J, Duan E K
State Key Laboratory of Reproductive Biology, Institute of Zoology, Academia Sinica, Beijing, P. R. China.
Cytokine. 2000 Nov;12(11):1676-82. doi: 10.1006/cyto.2000.0758.
Leukaemia inhibitory factor (LIF) is a pleiotrophic cytokine. Recent reports indicate that LIF is relevant to murine embryo implantation. In this work, results of indirect immunofluorescence under a confocal microscope illustrated that LIF was mainly located in the uterine lumen and uterine epithelial cells in pregnant mice on day 4. The number of embryos implanted in pregnant mice on day 8 decreased significantly after injection of 3 microg LIF antibodies into a uterine horn (P<0.001), which demonstrated again that LIF is a critical factor for embryo implantation. In a co-culture system, LIF (0.1 ng/ml, 1 ng/ml, 10 ng/ml and 100 ng/ml) significantly enhanced the blastocyst outgrowth after 24, 48 or 72 h of co-culture, and outgrowth areas after 72 h of co-culture. Conversely, 5 microg/ml and 10 microg/ml, but not 1 microg/ml, LIF antibodies decreased the percentage of blastocysts with outgrowth; only 10 microg/ml LIF antibody inhibited blastocyst outgrowth area significantly (P<0.001). However, neither LIF nor its antibodies changed embryo attachment. Analysis of correlation showed that the effects of LIF or its antibodies on the blastocyst outgrowth were dose-dependent. In summary, different pathways may exist to regulate the blastocyst attachment and outgrowth on a monolayer of uterine epithelial cells. LIF protein from the maternal uterus exerts an essential role in embryo implantation in the mouse, which is mediated by stimulating trophoblast outgrowth, but not by promoting the attachment.
白血病抑制因子（LIF）是一种多效性细胞因子。最近的报道表明，LIF与小鼠胚胎着床有关。在本研究中，共聚焦显微镜下的间接免疫荧光结果显示，LIF主要位于妊娠第4天的妊娠小鼠子宫腔和子宫上皮细胞中。向子宫角注射3μg LIF抗体后，第8天妊娠小鼠的着床胚胎数量显著减少（P<0.001），这再次证明LIF是胚胎着床的关键因子。在共培养系统中，LIF（0.1 ng/ml、1 ng/ml、10 ng/ml和100 ng/ml）在共培养24、48或72小时后显著增强了囊胚的孵出，并在共培养72小时后增加了孵出面积。相反，5μg/ml和10μg/ml（而非1μg/ml）的LIF抗体降低了有孵出的囊胚百分比；只有10μg/ml的LIF抗体显著抑制了囊胚孵出面积（P<0.001）。然而，LIF及其抗体均未改变胚胎附着。相关性分析表明，LIF或其抗体对囊胚孵出的影响呈剂量依赖性。总之，可能存在不同的途径来调节子宫上皮细胞单层上的囊胚附着和孵出。母体子宫中的LIF蛋白在小鼠胚胎着床中发挥着重要作用，这是通过刺激滋养层孵出介导的，而不是通过促进附着来实现的。
