Terakawa Jumpei, Wakitani Shoichi, Sugiyama Makoto, Inoue Naoko, Ohmori Yasushige, Kiso Yasuo, Hosaka Yoshinao Z, Hondo Eiichi
Laboratory of Animal Morphology and Function, Division of Biofunctional Development, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
J Reprod Dev. 2011 Dec;57(6):700-7. doi: 10.1262/jrd.11-048h. Epub 2011 Aug 12.
Leukemia inhibitory factor (LIF) is essential for embryo implantation in mice and plays an important role in other mammals including humans. Intraperitoneal (i.p.) injections with anti-LIF antibody (7.5 µg/g body weight, 3 times) between D3 (D1 = day of vaginal plug detection) and D4 effectively blocked embryo implantation; complete inhibition was achieved in C57BL/6J mice, and implantation was dramatically reduced in ICR mice (reduced to 27%). Normal rabbit IgG used as the control did not disturb embryo implantation. Anti-LIF antibody was localized not only in the stroma, but also in the luminal epithelium and the glandular lumen after i.p. injections. Growth-arrested blastocysts were recovered from the uterus without any implantation sites in both strains. Blastocysts made contact with the LE on the antimesometrial side; however, uterine stromal cells did not undergo secondary decidual reaction, and the uterine lumen was open, even at D7. Several regions of decidualization in ICR mice treated with anti-LIF antibody were smaller than those of the control, and development of blastocysts was delayed. The expression of LIF-regulated genes, such as immune-responsive gene-1 and insulin-like growth factor binding protein-3, was significantly decreased in C57BL/6J mice treated with anti-LIF antibody compared with the control, but not in ICR mice. The present study demonstrated that simple ip injections of an antibody are sufficient to block one of the important factors involved in embryo implantation in mice, and this method should also be easily applicable to the investigation of other factors involved in implantation.
白血病抑制因子（LIF）对小鼠胚胎着床至关重要，在包括人类在内的其他哺乳动物中也发挥着重要作用。在第3天（第1天 = 检测到阴道栓的日子）至第4天之间腹腔注射抗LIF抗体（7.5μg/g体重，3次）可有效阻断胚胎着床；在C57BL/6J小鼠中实现了完全抑制，而在ICR小鼠中着床显著减少（降至27%）。用作对照的正常兔IgG不会干扰胚胎着床。腹腔注射后，抗LIF抗体不仅定位于基质，还定位于腔上皮和腺腔内。在两个品系的子宫中均回收了未着床的生长停滞囊胚。囊胚与子宫系膜对侧的腔上皮接触；然而，子宫基质细胞未发生继发性蜕膜反应，即使在第7天子宫腔仍开放。用抗LIF抗体处理的ICR小鼠中，几个蜕膜化区域比对照小鼠小，囊胚发育延迟。与对照相比，用抗LIF抗体处理的C57BL/6J小鼠中，LIF调节基因如免疫反应基因-1和胰岛素样生长因子结合蛋白-3的表达显著降低，但在ICR小鼠中未降低。本研究表明，简单的腹腔注射抗体足以阻断小鼠胚胎着床过程中涉及的重要因素之一，该方法也应易于应用于研究着床过程中涉及的其他因素。
