Activated platelets induce hypoxia-inducible factor-1a expression likely through transforming growth factor-1 in human endometrial stromal cells

Objective: Endometriosis is a common gynecological disease with an enigmatic pathogenesis. Recent studies suggest that the behavior of normal endometrial stromal cells can dramatically change under hypoxic conditions, which effectively turns them into endometriotic stromal cells. Because menstrual debris is not only hypoxic but may also contain platelet aggregates, at present, we aimed to approve that activated platelets could induce hypoxia-inducible factor-1a (HIF-1a) expression in endometrial stromal cells, signaling the presence of hypoxia. Methods: We evaluated the gene and protein expression levels of HIF-1a and its target gene erythropoietin (EPO) in both human endometriotic stromal cells (HESCs) and a human endometrial stromal cell line (ESCL) cocultured with or without activated platelets for 48 h. Results: We found that the gene and protein expression levels of HIF-1a and EPO in both HESC and ESCL were significantly increased after coculture with activated platelets. We also found that neutralization of transforming growth factor-1 completely abolishes this induction. Conclusions: Platelets can induce a hypoxic state in endometrial and endometriotic stromal cells, resulting in increased angiogenesis, as well as enhanced survival and proliferation. In conjunction with other roles that platelets play in the development of endometriosis, our findings further highlight the important roles of platelets in the development and initiation of endometriosis, shedding new light into the etiology of endometriosis.