A tissue-engineered human endometrial stroma that responds to cues for secretory differentiation, decidualization, and menstruation

Objective: To show the responsiveness of tissue-engineered human endometrial stroma to combinations of hormones that mimic the secretory and menstrual phases of the cycle. Design: In vitro experimental study. Setting: University uterine biology research laboratory. Patient(s): None. Intervention(s): Telomerase immortalized human endometrial stromal cells cultured in monolayers (two-dimensional, 2D) or encapsulated in a collagen I hydrogel (three-dimensional, 3D) to create a simplified tissue-engineered stroma were exposed to hormone treatments mimicking early and late secretory phases, decidualization, and steroid withdrawal conditions to recapitulate menstruation. Main Outcome Measure(s): Morphologic and biochemical markers of decidualization and collagenase activity. Result(s): The 3D tissue can manifest changes in morphology and biochemical markers of decidualization similar to 2D culture and characteristic of endometrial stroma in vivo. Unlike 2D culture, the 3D tissue responded to steroid withdrawal by increased collagenase activity and tissue breakdown. Conclusion(s): Three-dimensional tissue-engineered endometrial stroma can mimic secretory and menstrual phases of the cycle and may be useful for studying uterine receptivity and menstruation in a physiological endocrine environment. (Fertil Steril((R)) 2012; 97: 997-1003. (C) 2012 by American Society for Reproductive Medicine.)