Low doses of celecoxib stimulate human endometrium growth in a three-dimensional culture model

ABSTRACT

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. In this experimental study, normal human endometria [n=10] obtained from reproductive age women were cut into 1x1 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 micro M 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. The growth scores were as follows control [1.37 +/- 0.16], 1 micro M [1.96 +/- 0.28], 10 micro M [2.01 +/- 0.25], and 50 micro M [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 micro M], 42.67 +/- 7.27% [10 micro M] and 23.44 +/- 4.03% [50 micro M], which were not significantly different from each other. Lower celecoxib concentrations had stimulatory effects on the growth of normal endometrium