Cumulus cell-released tumor necrosis factor (TNF)-α promotes post-ovulatory aging of mouse oocytes

Although previous studies indicated that cumulus cells (CCs) accelerate oocyte aging by releasing soluble factors, the factors have yet to be characterized. While demonstrating that CCs promoted oocyte aging by releasing soluble Fas ligand (sFasL), our recent study suggested that CCs might secrete other factors to mediate oocyte aging as well. This study tested whether CCs accelerate oocyte aging by secreting tumor necrosis factor (TNF)-alpha. The results showed that mouse CCs undergoing apoptosis released soluble TNF-alpha (sTNF-alpha) during in vitro aging. While ethanol activation rates were higher, the maturation-promoting factor (MPF) activity was lower significantly after culture of cumulus-denuded oocytes (DOs) in medium conditioned with CCs for 36 h than in medium conditioned for 24 h. Aging mouse oocytes expressed TNF-receptor 1. The CCs released equal amounts of sTNF-alpha and sFasL during aging in vitro, and the TNF-alpha-knockdown CCs secreted less sFasL than the control CCs did. Treatment of DOs in vitro with sTNF-alpha significantly accelerated their aging. The aging-promoting effect of sTNF-alpha was significantly reduced in TNF-alpha-knocked-down CCs and in CCs from the TNF-alpha-knockout mice. It is concluded that mouse CCs accelerate oocyte aging by secreting sTNF-alpha as well as sFasL.