Embryonic β-Catenin Is Required for Priming of the Uterus to Implantation

Repeated implantation failure is a major cause of infertility among healthy women. Uterine beta-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 Ctnnb1deficient (Ctnnb1(Delta/Delta)) embryos. Ctnnb1(Delta/Delta) embryos were produced by intercrossing mice bearing Ctnnb1-deficient eggs and sperms. We found that Ctnnb1(Delta/Delta) 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(Delta/Delta) blastocysts. Furthermore, CDX2, a transcription factor that determines the fate of trophectoderm cells, was not observed in Ctnnb1(Delta/Delta) blastocysts. Intrauterine injection with uterine fluids (from control mice) and recombinant mouse leukemia inhibitory factor proteins rescued the uterine response to Ctnnb1(Delta/Delta) 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. (c) 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.

Automated summary

Repeated implantation failure is a common cause of infertility in healthy women. The role of embryonic CTNNB1 in implantation is not well understood. Using mouse models, researchers found that Ctnnb1(Delta/Delta) embryos developed to the blastocyst stage but were subsequently resorbed, leaving empty decidual capsules. The absence of leukemia inhibitory factor and CDX2 in Ctnnb1(Delta/Delta) blastocysts indicates the importance of embryonic CTNNB1 in the secretion of blastocyst-derived factors and the proper development of trophectoderm cells. Intrauterine injection of uterine fluids and leukemia inhibitory factor proteins rescued the uterine response to Ctnnb1(Delta/Delta) blastocysts, suggesting a potential therapeutic approach for improving implantation. These findings contribute to a better understanding of the pathogenesis of repeated implantation failure.