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

Mizuki Sone, Kazunori Oyama, Yasuaki Mohri, Ryotaro Hayashi, Hans Clevers, Katsuhiko Nishimori

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 (Lgr4K5 KO). Interestingly, the Lgr4K5 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 Lgr4K5 KO female mice. Histological analysis revealed that the uteri of Lgr4K5 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 Lgr4K5 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 Lgr4K5 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.-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.

Original languageEnglish
Pages (from-to)4917-4928
Number of pages12
JournalFASEB Journal
Volume27
Issue number12
DOIs
Publication statusPublished - 2013 Dec 1

Keywords

  • Foxa2
  • Lif
  • Wnt signaling

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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