The signaling pathways by which the Fas/FasL system accelerates oocyte aging

Abstract

Abstract:In spite of great efforts, the mechanisms for postovulatory oocyte aging are not fully understood. Although our previous work showed that the FasL/Fas signaling facilitated oocyte aging, the intra-oocyte signaling pathways are unknown. Furthermore, the mechanisms by which oxidative stress facilitates oocyte aging and the causal relationship between Ca 2+ rises and caspase-3 activation and between the cell cycle and apoptosis during oocyte aging need detailed investigations. Our aim was to address these issues by studying the intra-oocyte signaling pathways for Fas/FasL to accelerate oocyte aging. The results indicated that sFasL released by cumulus cells activated Fas on the oocyte by increasing reactive oxygen species via activating NADPH oxidase. The activated Fas triggered Ca 2+ release from the endoplasmic reticulum by activating phospholipase C-γ pathway and cytochrome c pathway. The cytoplasmic Ca 2+ rises activated calcium/calmodulin-dependent protein kinase II (CaMKII) and caspase-3. While activated CaMKII increased oocyte susceptibility to activation by inactivating maturation-promoting factor (MPF) through cyclin B degradation, the activated caspase-3 facilitated further Ca 2+ releasing that activates more caspase-3 leading to oocyte fragmentation. Furthermore, caspase-3 activation and fragmentation were prevented in oocytes with a high MPF activity, suggesting that an oocyte must be in interphase to undergo apoptosis.

BAPTA‐AM dramatically improves maturation and development of bovine oocytes from grade‐3 cumulus‐oocyte complexes

“…Calcium is a major signaling molecule that regulates many aspects of cellular function, including cell‐cycle progression (Machaty, ; Tosti, ), cell‐cycle arrest (Tripathi et al, ), and apoptosis (Berridge et al, ; Tiwari et al, ). A sustained increase in [Ca 2+ ] i levels beyond the normal physiologic range in oocytes triggers FAS‐ligand‐ and mitochondria‐mediated apoptosis in several mammalian species (Tiwari, Prasad, Shrivastav, & Chaube, ; Zhu et al, ). Previous studies suggested that the physiological role of calcium depends on its intracellular concentration (Homa, ; Naik & Pardasani, ; Tosti, ; Whitaker, ), resulting in improved developmental competence or fragmentation/apoptosis (Takahashi et al, ; Takahashi, Saito, Hiroi, Doi, & Takahashi, ).…”

Calcium Signaling During Meiotic Cell Cycle Regulation and Apoptosis in Mammalian Oocytes

“…These studies suggest that high level of [Ca ++ ]i trigger generation of ROS and mitochondria‐mediated apoptosis in mammalian oocytes. The involvement of increased [Ca ++ ]i level has also been reported to trigger Fas ligand‐mediated apoptosis in mouse oocytes (Zhu et al, ).…”

“…Growing body of evidences suggest that sustained high cytosolic free Ca ++ level induces CaMKII activity (Olofsson et al, ; Zhu et al, ) and trigger generation of ROS (Tripathi and Chaube, ) sufficient enough to cause oxidative stress (OS) in aged oocytes cultured in vitro (Gordo et al, ; Chaube et al, ; Martin‐Romero et al, ; Tripathi and Chaube, ). Further, CaMKII activates Wee 1 that induces Thr14/Tyr15 phosphorylation of Cdk1 and cyclin B1 degradation leading to MPF destabilization (Kubiak et al, ; Oh, ).…”

“…Further, CaMKII activates Wee 1 that induces Thr14/Tyr15 phosphorylation of Cdk1 and cyclin B1 degradation leading to MPF destabilization (Kubiak et al, ; Oh, ). The sustained reduced level of stabilized MPF mediates apoptosis in aged oocytes cultured in vitro (Tripathi and Chaube, , ,; Zhu et al, ).…”

“…The increased cytochrome c activates upstream and downstream caspases in mouse oocytes (Liu et al, ; Zhang and Fissore, ). The caspase‐3 disrupt the histoarchitecture of oocyte by disrupting the structural and regulatory proteins, which results several biochemical and morphological changes during oocyte apoptosis (Chaube et al, , ,; Tripathi et al, , , ; Tiwari et al, , ; Zhu et al, ) (Fig. ).…”