Resveratrol inhibits development of experimental endometriosis and induces apoptosis of endometrial stroma

Abstract

OBJECTIVE: Resveratrol (RES), a polyphenol abundant in red grapes, has antioxidant, anti-proliferative and anti-inflammatory properties. Pathophysiology of endometriosis involves ectopic attachment and proliferation of endometrial tissues, oxidative stress and inflammation. This study evaluated effects of RES on a nude mouse model of endometriosis and on cultures of human endometrial stromal cells (HEC). DESIGN: In vitro and in vivo experiments. MATERIALS AND METHODS: Human proliferative phase endometrial biopsies were established as organ cultures or used for HEC isolation. To establish endometriosis in the ovariectomized nude mouse, endometrial tissues were maintained in 1 nM estradiol (E) for 24 hrs and subsequently injected intraperitoneally. Mice (N=12) were randomly assigned to RES Group or Control Group. RES Group received E (8 μg, silastic capsule implants) plus RES (5.9 mg/kg per day) by gavage for 10 days. Control mice received E+vehicle. The animals were then sacrificed and endometrial implants were measured and stained (TUNEL) for apoptosis. Studies of HEC evaluated effects of RES (30-100 μM) on apoptosis by detection of caspases 3/7. RESULTS: Mice treated with RES had significantly lower number and volume of endometrial implants: Control Group had on average 2.5±0.3 lesions/animal while mice treated with RES had 74% fewer lesions (0.6±0.2/animal; P<0.001). Average volume of implants was 11.5±1.5 mm3/animal in the Control Group and was 88% lower in RES Group (1.4±1.1 mm3; P=0.0003). TUNEL staining of implants from RES Group was significantly greater than that from Control mice. In cultures of HEC, RES induced a concentration dependent wave of apoptosis with maximum expression of caspases 3/7 at 48 hours increased 18-fold above control (P<0.001). CONCLUSIONS: RES significantly reduced the number and size of endometrial implants in the nude mouse model of endometriosis as well as induced HEC apoptosis. The present findings may lead to the development of novel treatments of endometriosis involving RES.