A 3D endometrial organotypic model simulating the acute inflammatory decidualisation initiation phase with epithelial induction of the key endometrial receptivity marker, integrin αVβ3.

study questionIs it possible to develop a simplified physiological SUMMARY ANSWER: We present a new concept to investigate endometrial receptivity, with a 3D organotypic co-culture model to simulate an early and transient acute autoinflammatory decidual status that resolves in the induction of a receptive endometrial phenotype. WHAT IS KNOWN ALREADY: Embryo implantation is dependent on a receptive uterine environment. Ovarian steroids drive post-ovulation structural and functional changes in the endometrium, which becomes transiently receptive for an implanting conceptus, termed the 'window of implantation', and dysregulation of endometrial receptivity is implicated in a range of reproductive, obstetric, and gynaecological disorders and malignancies. The interactions that take place within the uterine microenvironment during this time are not fully understood, and human studies are constrained by a lack of access to uterine tissue from specific time-points during the menstrual cycle. Physiologically relevant STUDY DESIGN SIZE DURATION: We conducted an PARTICIPANTS/MATERIALS SETTING

methodsAn endometrial stromal cell (ESC) line, and endometrial epithelial cells (EECs) isolated from endometrial biopsy tissue and expanded MAIN RESULTS AND THE ROLE OF CHANCE: A transient up-regulation of the interleukin-33 receptor protein, ST2L, was observed in ESCs, indicating a transient autoinflammatory decidual response to the hormonal stimulation, known to induce receptivity gene expression in the overlying epithelium. Hormonal stimulation increased the EEC protein levels of the key marker of endometrial receptivity, integrin αVβ3 (n = 8; * LIMITATIONS REASONS FOR CAUTION: This simplified WIDER IMPLICATIONS OF THE

findingsThe 3D endometrial organotypic model presented here may offer a valuable tool for investigating a range of reproductive, obstetric, and gynaecological disorders, to improve outcomes for assisted reproductive technologies, and for the development of advances in contraceptive methods. STUDY FUNDING/COMPETING INTERESTS: This work was supported in part by a Medical Research Council Centre Grant (project reference MR/N022556/1). R.F. was the recipient of a Moray Endowment award and a Barbour Watson Trust award. C.-J.L. is a Royal Society of Edinburgh Personal Research Fellow, funded by the Scottish Government. The authors have no conflicts of interest to declare.