Jia Guo, Jiawei Lyu, Zili Gao, Tan Jia, LeYun Wang, Jingxi Dong, Zhen Gu, Shen Ji, Wei Li, Hongmei Wang, Jinglei Zhai Jinglei Zhai, Leqian Yu, Guihai Feng, Qi Zhou, Qi Gu
Embryo development undergoes critical morphological transformations post-implantation, largely driven by the complex and dynamic microenvironment of the uterus. Despite advances, current 3D culture models inadequately recapitulate the uterine environment necessary for studying embryo-uterus interactions. In this work, we engineer a hydrogel inspired by the properties of the decidua, incorporating Matrigel to support blastocyst implantation and embryo development in vitro. Our findings reveal that embryos cultured within this hydrogel system successfully progress to an early organogenesis-like stage, including the development of first and second heart fields, mimicking natural embryogenesis. Moreover, we identify that the mechanical properties, particularly stress relaxation, play a crucial role in facilitating focal adhesion (FA) formation between the trophoblast and the hydrogel. Additionally, the degradation of the hydrogel by embryo-secreted metalloproteinases (MMP2 and MMP9) creates a favorable environment for continued embryonic growth and development. These insights contribute to a deeper understanding of how the external environment regulates embryo development and offer an enhanced approach for in vitro embryo culture. The complex interactions between the uterus microenvironment and the embryo during development are not fully understood. Here, authors engineer a 3D hydrogel culture system to investigate how the physical and biochemical properties of the uterine microenvironment impact embryo development in vitro.