IGF-1 promotes trophectoderm cell proliferation of porcine embryos by activating the Wnt/β-catenin pathway

Abstract

Background: Insulin-like growth factor 1 (IGF-1) influences various aspects of embryogenesis, including embryonic development. This study investigated the effects of IGF-1 on early embryonic development in pig embryos, focusing on its interaction with the Wnt/β-catenin signaling pathway, a key regulator of cell adhesion and proliferation. Methods: Porcine embryos were used for experiments with chemical treatments to study blastocyst development and underlying mechanism. Apoptosis, immunochemistry, gene expression, and protein quantification were performed, with statistical significance assessed. Results: IGF-1 treatment during the early stages of embryonic development significantly enhanced developmental parameters, in particular blastocyst formation rates. Interestingly, IGF-1 increased trophectoderm (TE) cell proliferation. The TE is an essential component of the blastocyst, maintaining its structure. Successful development of pig embryos was dependent on the proper formation and function of the TE. IGF-1 upregulated the expression of functional proteins related to TE differentiation and tight junctions. Notably, these effects were more pronounced when IGF-1 treatment was performed during the last 3 days of embryonic development (days 3-6) compared to the first 3 days (days 0-3). In addition, we found that IGF-1 promoted activation of the Wnt/β-catenin signaling pathway, including increasing β-catenin levels and related gene expression. To confirm the interaction between IGF-1 signaling and the Wnt/β-catenin pathway in TE development, embryos were cultured with picropodophyllin, an IGF-1 receptor inhibitor. Picropodophyllin suppressed developmental parameters, β-catenin levels, TE cell differentiation, and tight junction formation. These effects were successfully rescued by IGF-1 and the Wnt/β-catenin signaling activator ChiR99021. Conclusion: Our findings provide new insights into the interaction between IGF-1 and the Wnt/β-catenin signaling pathway during embryogenesis and highlight the potential of IGF-1 to improve reproductive outcomes by enhancing TE formation and quality.