Resveratrol Inhibits Development of Experimental Endometriosis In Vivo and Reduces Endometrial Stromal Cell Invasiveness In Vitro1

Abstract

Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with antiproliferative and anti-inflammatory properties. Our objective was to study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with 17β-estradiol (8 mg, silastic capsule implants) alone (n = 16) or with resveratrol (6 mg/mouse; n = 20) for 10-12 and 18-20 days beginning 1 day after tissue injection. Mice were killed and endometrial implants were evaluated. A Matrigel invasion assay was used to examine the effects of resveratrol on HES cells. We assessed number and size of endometriotic implants in vivo and Matrigel invasion in vitro. Resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10-30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis.

Targeting oxidative stress to treat endometriosis

“…In continuation to the positive reported effect of resveratrol on endometriosis [101], similar encouraging results of reduction in endometrial lesions size, cell proliferation, vascularization, inflammation, OS and lipid peroxidation markers were recently reported in several animal studies [102][103][104][105][106].…”

“…Resveratrol Bayoglu Tekin Y et al [105] Animal study Reduction of endometriotic lesion volume, histopathological grade, immunoreactivity to mmp2, mmp9 and VEGF, plasma and PF levels of IL-6, IL-8 and TNF-a Down-regulation of pro-inflammatory cytokines induction of apoptosis and promotion of cellular proliferation and differentiation, decrease in mmp2 and mmp9 activities, suppressed microvessel activity Bruner-Tran KL et al [101] In vitro + In vivo Reduction of number of endometrial implants, total volume of lesions (in vivo) and concentration-dependent reduction of invasiveness in human endometrial stromal cells (in vitro)…”

Is resveratrol a potential substitute for leuprolide acetate in experimental endometriosis?

“…Brunner-Tran et al first reported the therapeutic effect of resveratrol in an experimental endometriosis model by showing that it decreased endometrial cell proliferation and increased apoptosis [21]. Ricci et al [22] demonstrated both an increase in cell death and the antiangiogenic effects of resveratrol in an endometriosis model and human endometrial cell culture.…”

Periostin Enhances Migration, Invasion, and Adhesion of Human Endometrial Stromal Cells Through Integrin-Linked Kinase 1/Akt Signaling Pathway

“…Currently, there is no known cure for endometriosis and treatment aims at relieving pains, ameliorating infertility, eliminating lesions, and preventing recurrence. The available therapies are surgical excision and various medical treatments, which include gonadotropin-releasing hormone analogs, aromatase inhibitors, and progestins, 5 However, these medical therapies are not suitable long term due to their numerous side effects, such as massive hemorrhage, perimenopausal stage symptoms, and liver dysfunction. [6][7][8] Moreover, the recurrence rate of endometriosis is still high following conservative surgery, unless patients accepted hysterectomy or reached menopause.…”