title: LGR4 expressed in uterine epithelium is necessary for uterine gland development and contributes to decidualization in mice.
abstract: 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.
authors: 3Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, 1-1, Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan. knishimori@m.tohoku.ac.jp.
authors: Mizuki
authors: M
authors: Sone
authors: Kazunori
authors: K
authors: Oyama
authors: Yasuaki
authors: Y
authors: Mohri
authors: Ryotaro
authors: R
authors: Hayashi
authors: Hans
authors: H
authors: Clevers
authors: Katsuhiko
authors: K
authors: Nishimori
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003656:Decidua / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000473:pathology*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D014599:Uterus / Q000002:abnormalities / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: C496200:LGR4 protein, mouse; D053605:Leukemia Inhibitory Factor; D043562:Receptors, G-Protein-Coupled
keywords: Foxa2; Lif; Wnt signaling