Low Doses of Celecoxib Stimulate Human Endometrium Growth in A Three-Dimensional Culture Model

Background: The endometrium plays a pivotal role in implantation and pregnancy. Cyclooxygenase II (COX-2) has an important function in biological processes such as cell proliferation and inflammation. Celecoxib is a selective inhibitor of COX-2 with numerous pharmacologic functions. The aim of present study is to investigate the effects of celecoxib on the human endometrium in a three-dimensional (3D) culture model. Materials and Methods: In this experimental study, normal human endometria (n=10) obtained from reproductive age women were cut into 1×1 mm sections. Endometrial explants were placed between two layers of fibrin gel. To create the fibrin gel, we poured a thin layer of fibrinogen solution [3 mg/ml in medium 199 (M199)] into each well of a 24-well culture dish and added thrombin enzyme. Endometrial fragments were placed in the center of each well and covered with a second layer of fibrinogen solution. M199 supplemented with L-glutamine, fetal bovine serum (FBS, 5%) and antibiotics were added to each well. The media in each experimental well contained either1, 10 or 50 µM of celecoxib. At the end of the study, we calculated endometrial tissue growth changes by scoring methods and determined the percentage of angiogenesis. Data were analyzed by the Kruskal-Wallis method. P < 0.05 was considered significant. Results: The growth scores were as follows: control (1.37 ± 0.16), 1 µM (1.96 ± 0.28), 10 µM (2.01 ± 0.25), and 50 µM (1.17 ± 0.14) celecoxib, all of which were significantly different. The angiogenesis percentages were: 25.56 ± 6.72% (control), 31.98 ± 6.18% (1 µM), 42.67 ± 7.27% (10 µM) and 23.44 ± 4.03% (50 µM), which were not significantly different from each other. Conclusion: Lower celecoxib concentrations had stimulatory effects on the growth of normal endometrium.