Kim Min Ju, Kang Hyo-Gu, Jeon Se-Been, Yun Ji Hyeon, Choi Eun Young, Jeong Pil-Soo, Song Bong-Seok, Kim Sun-Uk, Cho Seong-Keun, Sim Bo-Woong
Futuristic Animal Resource & Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
Department of Animal Science, College of Natural Resources & Life Science, Pusan National University, Miryang, Republic of Korea.
Cell Commun Signal. 2025 Apr 20;23(1):188. doi: 10.1186/s12964-025-02191-2.
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.
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.
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.
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.
胰岛素样生长因子1(IGF-1)影响胚胎发生的各个方面,包括胚胎发育。本研究调查了IGF-1对猪胚胎早期胚胎发育的影响,重点关注其与Wnt/β-连环蛋白信号通路的相互作用,该信号通路是细胞黏附和增殖的关键调节因子。
使用猪胚胎进行化学处理实验,以研究囊胚发育及其潜在机制。进行了细胞凋亡、免疫化学、基因表达和蛋白质定量分析,并评估了统计学意义。
胚胎发育早期的IGF-1处理显著提高了发育参数,特别是囊胚形成率。有趣的是,IGF-1增加了滋养外胚层(TE)细胞的增殖。TE是囊胚的重要组成部分,维持其结构。猪胚胎的成功发育取决于TE的正常形成和功能。IGF-1上调了与TE分化和紧密连接相关的功能蛋白的表达。值得注意的是,与胚胎发育的前3天(第0 - 3天)相比,在胚胎发育的最后3天(第3 - 6天)进行IGF-1处理时,这些影响更为明显。此外,我们发现IGF-1促进了Wnt/β-连环蛋白信号通路的激活,包括增加β-连环蛋白水平和相关基因表达。为了证实IGF-1信号与Wnt/β-连环蛋白通路在TE发育中的相互作用,用IGF-1受体抑制剂鬼臼苦素培养胚胎。鬼臼苦素抑制了发育参数、β-连环蛋白水平、TE细胞分化和紧密连接的形成。IGF-1和Wnt/β-连环蛋白信号激活剂ChiR99021成功挽救了这些影响。
我们的研究结果为胚胎发生过程中IGF-1与Wnt/β-连环蛋白信号通路之间的相互作用提供了新的见解,并强调了IGF-1通过增强TE形成和质量来改善生殖结果的潜力。