LGR4 expressed in uterine epithelium is necessary for uterine gland development and contributes to decidualization in mice

<jats:p> In previous work we generated mice with a tissue specific ablation of a leucine‐rich repeat containing G‐protein‐coupled receptor 4 ( <jats:italic>Lgr4</jats:italic> ) using the Keratin‐5 ( <jats:italic>K5</jats:italic> ) Cre transgenic mouse strain ( <jats:italic>Lgr4</jats:italic> <jats:sup>K5 KO</jats:sup> ). Interestingly, the <jats:italic>Lgr4</jats:italic> <jats:sup>K5 KO</jats:sup> 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 <jats:italic>Lgr4</jats:italic> <jats:sup>K5 KO</jats:sup> female mice. Histological analysis revealed that the uteri of <jats:italic>Lgr4</jats:italic> <jats:sup>K5 KO</jats:sup> mice displayed altered epithelial differentiation characterized by a reduction in the number of uterine glands. Furthermore, <jats:italic>Lgr4</jats:italic> deletion led to the reduced expression of morphoregulatory genes related to the Wnt signaling pathway. Additionally, the uteri of the <jats:italic>Lgr4</jats:italic> <jats:sup>K5 KO</jats:sup> 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 <jats:italic>Lgr4</jats:italic> <jats:sup>K5 KO</jats:sup> 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.—Sone, M., Oyama, K., Mohri, Y., Hayashi, R., Clevers, H., Nishimori, K., LGR4 expressed in uterine epithelium is necessary for uterine gland development and contributes to decidualization in mice. FASEB J. 27, 4917–4928 (2013). <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://www.fasebj.org">www.fasebj.org</jats:ext-link> </jats:p>