Comparison of raloxifene effect on the growth and angiogenesis of human endometrium of healthy and endometriosis subjects: An in vitro three-dimensional tissue culture model

Abstract

Introduction: Raloxifene (Ral) is the oldest SERM (selective oestrogen receptor modulators) for treatment of breast cancer and osteoporosis. Its oestrogen-modulating effects have been shown in breast and uterus. Since there is little available data on direct Ral effect on the human endometrium, the aim of present study was to investigate the Ral effect on the growth and angiogenesis of the human endometrium of healthy and endometriosis subjects in an in vitro three-dimensional (3D) tissue culture model. Material and methods: Endometrial biopsies from healthy (n = 9) and endometriosis (n = 7) patients (endometriotic) were taken and were cut into 1 × 1 mm fragments and implanted between two layers of fibrin jell made by fibrinogen solution (3 mg/ml in medium 199+thrombin). Tissue cultures were performed in 24-wel culture plates. Each biopsy was divided into control wells which received M199 supplemented with FBS (5%) and experimental wells which received same media containing one of raloxifene doses (0.1, 1 and 10 μM). Endometrial tissues were photographed at the beginning and the end of the study period (21 days). Tissue growth and angiogenesis were determined by a scoring system. Results: In control (0), 0.1, 1 and 10 μM Ral, the growth score of normal human endometrial tissues were 1.99, 1.72, 1.53 and 1.12 (p = 0.02) and angiogenesis percent were 29.6%, 31.28%, 33% and 11.5%. The Growth scores of the endometriotic endometrium were 1.92, 1.82, 1.92 and 1.1 (p = 0.008) and angiogenesis percent were 36.6%, 16.6%, 44% and 12.5% respectively. Conclusion: Raloxifene showed a different dose dependent effect on endometrial and endometriotic tissue.