3Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, 1-1, Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
FASEB J. 2013 Dec;27(12):4917-28. doi: 10.1096/fj.13-232215. Epub 2013 Aug 23.
In previous work we generated mice with a tissue specific ablation of a leucine-rich repeat containing G-protein-coupled receptor 4 (Lgr4) using the Keratin-5 (K5) Cre transgenic mouse strain (Lgr4(K5 KO)). Interestingly, the Lgr4(K5 KO) female mice were subfertile, and their embryos had impaired development. Notably, the contributions of uterine development to the subfertility phenotype were not elucidated in the previous report. In a readdress, the following study explores uterine aberration in Lgr4(K5 KO) female mice. Histological analysis revealed that the uteri of Lgr4(K5 KO) mice displayed altered epithelial differentiation characterized by a reduction in the number of uterine glands. Furthermore, Lgr4 deletion led to the reduced expression of morphoregulatory genes related to the Wnt signaling pathway. Additionally, the uteri of the Lgr4(K5 KO) mice lost the ability to undergo induced decidualization. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis and administration of recombinant leukemia inhibitory factor (LIF) demonstrated that the impaired decidualization in Lgr4(K5 KO) mice resulted from the decreased secretion of LIF concurrent with a reduction in uterine gland count. Thus, we propose that LGR4 contributes to uterine gland development, which supports decidualization during pregnancy.
在之前的工作中，我们使用角蛋白 5 (K5) Cre 转基因小鼠品系（Lgr4(K5 KO)）特异性敲除富含亮氨酸重复序列的 G 蛋白偶联受体 4 (Lgr4)，生成了一组小鼠。有趣的是，Lgr4(K5 KO)雌性小鼠表现出生育力下降，其胚胎发育受损。值得注意的是，之前的报告并未阐明子宫发育对生育力下降表型的贡献。在重新研究中，本研究探讨了 Lgr4(K5 KO)雌性小鼠的子宫异常。组织学分析显示，Lgr4(K5 KO)小鼠的子宫表现出上皮分化改变的特征，表现为子宫腺数量减少。此外，Lgr4 缺失导致与 Wnt 信号通路相关的形态发生调节基因表达减少。此外，Lgr4(K5 KO)小鼠的子宫失去了诱导蜕膜化的能力。定量逆转录聚合酶链反应 (qRT-PCR) 分析和重组白血病抑制因子 (LIF) 的给药表明，Lgr4(K5 KO) 小鼠蜕膜化受损是由于 LIF 分泌减少和子宫腺数量减少所致。因此，我们提出 LGR4 有助于子宫腺发育，这支持妊娠期间的蜕膜化。
