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

Abstract

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)-α. The results showed that mouse CCs undergoing apoptosis released soluble TNF-α (sTNF-α) 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-α and sFasL during aging in vitro, and the TNF-α-knockdown CCs secreted less sFasL than the control CCs did. Treatment of DOs in vitro with sTNF-α significantly accelerated their aging. The aging-promoting effect of sTNF-α was significantly reduced in TNF-α-knocked-down CCs and in CCs from the TNF-α-knockout mice. It is concluded that mouse CCs accelerate oocyte aging by secreting sTNF-α as well as sFasL.

The Effect of Lysophosphatidic Acid-supplemented Culture Medium on Human Immature Oocytes Matured in Vitro

“…In this study, transcriptome analysis revealed that only four differentially expressed genes were upregulated in the cumulus cells and only four were downregulated in oocytes, indicating that LPA had varying effects on the gene expression of cumulus cells and oocytes. KEGG pathway enrichment analysis revealed upregulated and downregulated genes in the cumulus cells that enrich the TNF signaling pathway, and the cumulus cells can release soluble TNF-α to promote oocyte aging (32). In our study, the upregulated genes in the cumulus cells enriched the insulin secretion pathway.…”

The effect of lysophosphatidic acid-supplemented culture medium on human immature oocytes matured in vitro

“…KEGG pathway enrichment analysis revealed upregulated and downregulated genes in the CCs that enrich the TNF signaling pathway, and the CCs can release soluble TNF-α to promote oocyte aging [24]. In our study, the upregulated genes in the CCs enriched the insulin secretion pathway.…”

The Role of Oxidative Stress and Natural Antioxidants in Ovarian Aging

“…Li et al demonstrated that oxidative stress induced bovine GC apoptosis by increasing the expression of cleaved caspase-3 and the Bax/Bcl-2 ratio as well as decreasing the expression of antioxidant enzymes (SOD2, glutathione peroxidase (GSH-Px)) ( Wang Y et al, 2019 ). In addition, excessive ROS in oocytes and GCs can induce the release of TNFα ( Kong et al, 2018 ; Miao et al, 2018 ). TNF-α binds to its death receptors (such as Fas and TNFR) and then activates the death receptor (extrinsic) pathway of apoptosis through Fas-associated death domain-dependent activation of caspase-8 ( Morgan et al, 2008 ; Guicciardi and Gores, 2009 ; Redza-Dutordoir and Averill-Bates, 2016 ).…”