Regulation of granulosa cell apoptosis by death ligand–receptor signaling

Abstract

Several hundred thousand primordial follicles are present in the mammalian ovary, however, only 1% develop to the preovulatory stage and finally ovulate. The remainder will be eliminated via a degenerative process called ‘atresia’. The endocrinological regulatory mechanisms involved in follicular development and atresia have largely been characterized but the precise temporal and molecular mechanisms involved in the regulation of these events remain unknown. Many recent studies suggest that apoptosis in ovarian granulosa cells plays a crucial role in follicular atresia. Notably, death ligand‐receptor interaction and subsequent intracellular signaling have been demonstrated to be the key mechanisms regulating granulosa cell apoptosis. In this review we provide an overview of granulosa cell apoptosis regulated by death ligand‐receptor signaling. The roles of death ligands and receptors [Fas ligand (FasL)]‐Fas, tumor necrosis factor α (TNFα)‐TNF receptor and TNFα‐related apoptosis‐inducing ligand (TRAIL)‐TRAIL receptor (TRAILR)] and intracellular death‐signal mediating molecules (Fas‐associated death domain protein), TNF receptor 1‐associated death domain protein, caspases, apoptotic protease‐activating factor 1, TNFR‐associated factor 2 and cellular FLICE‐like inhibitory protein in granulosa cells are discussed.

Changes in Expression and Localization of X-linked Inhibitor of Apoptosis Protein (XIAP) in Follicular Granulosa Cells During Atresia in Porcine Ovaries

“…54: [454][455][456][457][458][459] 2008) n mammalian ovaries, more than 99% of follicles disappear during follicular growth and development, and this appears to be primarily due to apoptosis of follicular granulosa cells, as the biochemical and morphological characteristics of apoptosis have been observed in the granulosa cells of atretic follicles [1][2][3]. Apoptotic stimuli and intracellular apoptosis-signal transduction pathways in granulosa cells have not yet been determined, and many researchers have attempted to confirm the primary trigger of apoptosis and how the intracellular apoptotic signal is transmitted in granulosa cells [4][5][6][7]. Many apoptosis-related factors are implicated in follicular atresia, including cell death ligands and receptors, intracellular pro-and anti-apoptotic molecules, cytokines and growth factors.…”

“…Apoptotic stimuli and intracellular apoptosis-signal transduction pathways in granulosa cells have not yet been determined, and many researchers have attempted to confirm the primary trigger of apoptosis and how the intracellular apoptotic signal is transmitted in granulosa cells [4][5][6][7]. Many apoptosis-related factors are implicated in follicular atresia, including cell death ligands and receptors, intracellular pro-and anti-apoptotic molecules, cytokines and growth factors.…”

“…Many apoptosis-related factors are implicated in follicular atresia, including cell death ligands and receptors, intracellular pro-and anti-apoptotic molecules, cytokines and growth factors. In particular, cell death ligand-receptor signaling has been revealed to be the dominant regulatory system for apoptosis in granulosa cells [4][5][6][7]. To date, two major intracellular-signal pathways in cell-death ligand and receptor-dependent apoptosis (type I and type II: mitochondrion-independent anddependent pathways, respectively) have been found [8][9][10][11][12].…”

Molecular Cloning of Porcine (Sus scrofa) Tumor Necrosis Factor Receptor 2

“…Our recent findings [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] have suggested that apoptosis in follicular granulosa cells plays a crucial role in the regulation of ovarian follicular atresia; however, the intracellular signal transduction pathway for apoptois in granulosa cells is still largely unknown [20,21]. Moreover, we have previously suggested that apoptosis and proliferation in granulosa cells are dominantly regulated by a cell death ligand and receptor system (TNF and TNFR superfamily members) [18][19][20][21]. In the granulosa cells of porcine ovarian follicles, TNFα acts as a cell proliferation factor but not as an apoptotic factor [13].…”

“…The TNFα-mediated apoptotic signaling pathway (TNFR1-dependent apoptosis) has been suggested to be as follows [1][2][3][4][5][6][7][8] In mammalian ovaries, more than 99.9% of follicles undergo a degenerative process known as "atresia", and only a few follicles selectively ovulate during ovarian follicular development and growth [15][16][17][18][19][20][21]. Our recent findings [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] have suggested that apoptosis in follicular granulosa cells plays a crucial role in the regulation of ovarian follicular atresia; however, the intracellular signal transduction pathway for apoptois in granulosa cells is still largely unknown [20,21]. Moreover, we have previously suggested that apoptosis and proliferation in granulosa cells are dominantly regulated by a cell death ligand and receptor system (TNF and TNFR superfamily members) [18][19][20][21].…”