Embryonic β-Catenin Is Required for Priming of the Uterus to Implantation.
Youki TakezawaMaki IwaiYukiko FujikiRyo YokomizoHarue KishigamiMami MiyadoNatsuko KawanoMitsutoshi YamadaMiyuki ShindoMiki SuzukiBan SatoDaiki KatanoShintaro KamijoToshio HamataniMamoru TanakaAkihiro UmezawaWoojin KangKenji MiyadoPublished in: Laboratory investigation; a journal of technical methods and pathology (2023)
Repeated implantation failure is a major cause of infertility among healthy women. Uterine β-catenin (CTNNB1) plays a critical role in implantation. However, the role of embryonic CTNNB1 during implantation remains unclear. We addressed this topic by analyzing mice carrying Ctnnb1-deficient (Ctnnb1 Δ/Δ ) embryos. Ctnnb1 Δ/Δ embryos were produced by intercrossing mice bearing Ctnnb1-deficient eggs and sperms. We found that Ctnnb1 Δ/Δ embryos developed to the blastocyst stage; thereafter, they were resorbed, leaving empty decidual capsules. Moreover, leukemia inhibitory factor, a uterine factor essential for implantation, was undetectable in Ctnnb1 Δ/Δ blastocysts. Furthermore, CDX2, a transcription factor that determines the fate of trophectoderm cells, was not observed in Ctnnb1 Δ/Δ blastocysts. Intrauterine injection with uterine fluids (from control mice) and recombinant mouse leukemia inhibitory factor proteins rescued the uterine response to Ctnnb1 Δ/Δ blastocysts. These results suggest that embryonic CTNNB1 is required for the secretion of blastocyst-derived factor(s) that open the implantation window, indicating that the uterine response to implantation can be induced using supplemental materials. Therefore, our results may contribute to the discovery of a similar mechanism in humans, leading to a better understanding of the pathogenesis of repeated implantation failure.
Keyphrases
- transcription factor
- acute myeloid leukemia
- cell proliferation
- epithelial mesenchymal transition
- bone marrow
- adipose tissue
- type diabetes
- small molecule
- polycystic ovary syndrome
- signaling pathway
- high glucose
- endoplasmic reticulum stress
- cell death
- endothelial cells
- wild type
- ultrasound guided
- cell free
- stress induced