Endometrial decidualization status modulates endometrial perivascular complexity and trophoblast outgrowth in gelatin hydrogels

Abstract

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 artificial endometrial perivascular niche embedded in gelatin methacrylol 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. Importantly, we demonstrate the engineered perivascular niche can be combined with epithelial cultures to form a stratified endometrial model. This artificial perivascular niche provides a well-characterized platform to investigate dynamic changes in angiogenesis in response to pathological and physiological endometrial states. TeaserWe describe an endometrial vessel model to understand endometrial vasculature in the menstrual cycle and pregnancy.