Lavranos T C, Rathjen P D, Seamark R F
Department of Obstetrics and Gynaecology, University of Adelaide, South Australia.
J Reprod Fertil. 1995 Nov;105(2):331-8. doi: 10.1530/jrf.0.1050331.
Myeloid leukaemia inhibitory factor (LIF) is expressed at highest concentrations in the maternal endometrial glands at about the stage of blastocyst implantation. LIF is also expressed by the extraembryonic membranes of the early mouse embryo. Embryos of different ages were cultured with, or without, LIF, and embryo growth in vivo and in vitro was examined to determine whether LIF is important for embryo development. Supplementing embryo culture media with 1000 U recombinant human LIF ml-1 increased the number of eight-cell mouse embryos developing beyond the hatched blastocyst stage in vitro from 62.1% to 85.1% (P < 0.05). LIF significantly increased the number of embryos hatching (33.8% versus 7.65% for controls 96 h after hCG injection, P < 0.001), completely hatching (85.1% versus 62.1%, P < 0.05), and exhibiting trophoblast outgrowth (13.5% versus 0% 120 h after hCG treatment, 85.1% versus 47.0% 144 h after hCG treatment, P < 0.001) in vitro. LIF-treated embryos also displayed a significantly greater area of trophoblast outgrowth than did controls as early as day 5 in culture (P < 0.005). These data show that LIF enhances mouse eight-cell embryo development in vitro, as seen by the accelerated rate of embryo hatching and trophoblast outgrowth. In addition, enhanced embryo survival in vivo is shown, following the transfer of LIF-treated embryos into a pseudopregnant recipient female. Expression of mRNA encoding LIF was detected in endometrial cells cultured in monolayer from uteri of day 3 pregnant females, explaining the known embryotrophic effects of endometrial coculture. This expression was not enhanced significantly by treatment with oestradiol (3.7 x 10(-5) mol l-1) or progesterone (3.2 x 10(-6) mol l-1) or both hormones. These results indicate that LIF could have a dual action in early embryogenesis as an embryotrophin and as a factor required for embryo implantation. Multiple roles for LIF are consistent with the expression of this factor at embryonic, extraembryonic and maternal sites during early embryogenesis.
髓系白血病抑制因子（LIF）在胚泡着床阶段，于母体子宫内膜腺中表达浓度最高。早期小鼠胚胎的胚外膜也表达LIF。将不同年龄的胚胎在有或无LIF的情况下进行培养，并检测胚胎在体内和体外的生长情况，以确定LIF对胚胎发育是否重要。在胚胎培养基中添加1000 U重组人LIF/ml，可使体外发育至孵化囊胚期后的八细胞小鼠胚胎数量从62.1%增加到85.1%（P<0.05）。LIF显著增加了胚胎孵化的数量（人绒毛膜促性腺激素（hCG）注射后96小时，LIF处理组为33.8%，对照组为7.65%，P<0.001）、完全孵化的数量（85.1%对62.1%，P<0.05）以及体外出现滋养层生长的数量（hCG处理后120小时，LIF处理组为13.5%，对照组为0%；hCG处理后144小时，LIF处理组为85.1%，对照组为47.0%，P<0.001）。在培养的第5天，LIF处理的胚胎滋养层生长面积就比对照组显著更大（P<0.005）。这些数据表明，LIF可促进小鼠八细胞胚胎在体外的发育，表现为胚胎孵化和滋养层生长速度加快。此外，将LIF处理的胚胎移植到假孕受体雌性体内后，显示出胚胎在体内的存活率提高。在第3天怀孕雌性子宫单层培养的子宫内膜细胞中检测到了编码LIF的mRNA的表达，这解释了子宫内膜共培养已知的胚胎营养作用。用雌二醇（3.7×10⁻⁵mol/l）或孕酮（3.2×10⁻⁶mol/l）或两种激素处理后，这种表达没有显著增强。这些结果表明，LIF在早期胚胎发生中可能具有双重作用，既是一种胚胎营养因子，也是胚胎着床所需的因子。LIF的多种作用与该因子在早期胚胎发生过程中在胚胎、胚外和母体部位的表达一致。
