Effects of tumor necrosis factor-α on cell proliferation, prostaglandins and matrix-metalloproteinases production in rat endometrial stromal cells cultured in vitro

Tumor necrosis factor-α (TNF-α) is known as a pluripotent cell mediator, and it is implicated in the control of uterine cell growth, differentiation and function during estrous cycle and pregnancy. In this study, we investigated the effect of TNF-α on endometrial stromal cells derived from rat uterus (rat endometrial stromal cells, RES). RES were isolated from rat endometrium at day 5 of pregnancy. Proliferation activities of RES were measured by using bromodeoxyuridine (BrdU) labeling kit, the productions of prostaglandin E2 (PGE₂) and prostaglandin F2α (PGF ₂α) were measured by enzyme immunoassay kits and the production of matrix metalloproteinases (MMPs) was analyzed by gelatin-zymography. TNF-α, as well as epidermal growth factor and fibroblast growth factor-2, significantly increased the proliferation activity of RES (P < 0.05). TNF-α selectively stimulated the production of PGE₂ in RES (P < 0.05), but not the production of PGF₂α. Additionally, TNF-α did not stimulate the production of MMPs in RES at the concentration of 5 ng/mL, compared with the control groups (P > 0.05). In conclusion, this study demonstrates several regulational functions of TNF-α on RES using in vitro culture system. The effects of TNF-α on proliferation and MMP production of RES have been shown for the first time. We believe that these results demonstrate part of the functions of TNF-α in endometrium and contribute to the better understanding of endometrial functions.