Resveratrol alleviates endometriosis via restoration of hypoxic milieu and inhibition of autoantibody deposition.

Endometriosis, a chronic disease that affects about 10% of women of reproductive age, is characterized by severe pain and growth of endometrium-like tissues outside the uteri. Although several theories have been advanced for the cause of endometriosis, no theory fully explains why endometriosis occurs. For this study, we strove to elucidate a new mechanism of endometriosis leading to establishment of a new therapeutic strategy for its treatment. In our murine endometriosis model, a marked hypoxic state was induced in the peritoneal cavity, as indicated by increased expression of HIF-1α in peritoneal exudate cells. Moreover, innate immune response, such as TLR4 and IL-1β expression, was upregulated. To restore the hypoxic milieu in endometriosis, we chose resveratrol (RSV), a natural polyphenolic compound, as a hypoxia-reducing agent. As expected, RSV administration decreased the number of HIF-1α-positive cells. Furthermore, RSV administration reduced the size and weight of endometriotic lesions significantly. However, RSV administration did not change TLR4 and IL-1β expression levels in peritoneal exudate cells. In the process of seeking mechanisms of endometriosis other than TLR4-dependent and IL-1β-dependent pathways, we detected autoantibody deposition in endometriotic lesions. In endometriotic lesions from RSV-administered mice, accumulation of autoantibodies was inhibited compared to a control group. As described herein, we proposed a new concept by which autoantibody deposition can cause endometriosis, raising the possibility of RSV as a promising therapeutic option for endometriosis.