The differentiation of stromal cell fibroblasts into the specialised decidua of the placenta is a progesterone-dependent process. To address the question of whether the human endometrial vasculature plays an active role in promoting stromal differentiation, primary human endometrial stromal cells were cultured for 14 days with primary uterine microvascular endothelial cells in a microfluidic organ-on-chip model of the endometrium. Cultures were maintained with oestradiol and a progestin, with or without continuous laminar perfusion to mimic blood flow-derived haemodynamic forces. Decidualisation in the microfluidic model was examined morphologically and biochemically. A significantly enhanced stromal decidualisation response was observed in the cocultures when the endothelial cells were stimulated with haemodynamic forces (e.g. laminar shear stress) due to controlled microfluidic perfusion. Furthermore, the enhanced progestin-driven stromal differentiation was mediated via cyclooxygenase-2 and the paracrine action of prostaglandin E2 and prostacyclin. Overall, these results suggest that the vascular endothelium plays an important
physiological role during the early events of perivascular decidualisation in human endometrium.
Hemodynamic forces enhance decidualization via endothelial-derived prostaglandin E2 and prostacyclin in a microfluidic model of the human endometrium
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