The endometrium undergoes rapid cycles of vascular growth, remodeling, and breakdown during the menstrual cycle and pregnancy. Decidualization is an endometrial differentiation process driven by steroidal sex hormones that is critical for blastocyst-uterine interfacing and blastocyst implantation. Certain pregnancy disorders may be linked to decidualization processes. However, much remains unknown regarding the role of decidualization and reciprocal trophoblast-endometrial interactions on endometrial angiogenesis and trophoblast invasion. Here, we report an engineered endometrial microvascular network embedded in gelatin methacryloyl hydrogels that displays morphological and functional patterns of decidualization. We show vessel complexity and soluble factor secretion are sensitive to decidualization and affect trophoblast motility. We also show that in our system, the signaling between endometrial and trophoblast cells was not bi-directional. Although endometrial microvascular network decidualization status influences the activity of trophoblast cells, trophoblast cells do not appear to influence structural changes in the endometrial microvascular network cultures. This finding has interesting implications as to the control of early stages of trophoblast motility from the endometrium but no marked early changes in its microvascular architecture in response to initial trophoblast implantation. These findings add to a growing literature that the endometrium has biological agency in the uterine-trophoblast interfacing process during implantation. Finally, we demonstrate the engineered microvascular networks can be combined with epithelial cultures to form a stratified endometrial tri-culture model. These endometrial microvascular networks provide a well-characterized platform to investigate dynamic changes in angiogenesis in response to pathological and physiological endometrial states.

Please see the linked manuscript for the most detailed methods section. The data were collected at the University of Illinois Urbana-Champaign, processed using a personal laptop computer (Mac) if necessary, and subsequently included in the manuscript.