Role of Cell-Death Ligand-Receptor System of Granulosa Cells in Selective Follicular Atresia in Porcine Ovary

Inoue, N.; Matsuda, Fuko; Goto, Yasufumi; Manabe, Noboru

doi:10.1262/jrd.10-198e

Cited by 72 publications

(50 citation statements)

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“…1D), and those follicles will then be eliminated. Morphologically, apoptosis is induced in granulosa cells located in the inner surface of the granulosa layer, but not in cumulus cells, oocytes or inner or extra theca layers in the early stages of atresia [6], indicating an initiating role of granulosa cell apoptosis in follicular atresia [7,8] (Fig. 1B).…”

Section: Regulation Of Follicular Growth and Atresia By Granulosa Cellsmentioning

confidence: 98%

Follicular Growth and Atresia in Mammalian Ovaries: Regulation by Survival and Death of Granulosa Cells

et al. 2012

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Abstract. The mammalian ovary is an extremely dynamic organ in which a large majority of follicles are effectively eliminated throughout their reproductive life. Due to the numerous efforts of researchers, mechanisms regulating follicular growth and atresia in mammalian ovaries have been clarified, not only their systemic regulation by hormones (gonadotropins) but also their intraovarian regulation by gonadal steroids, growth factors, cytokines and intracellular proteins. Granulosa cells in particular have been demonstrated to play a major role in deciding the fate of follicles, serving molecules that are essential for follicular growth and maintenance as well as killing themselves by an apoptotic process that results in follicular atresia. In this review, we discuss the factors that govern follicular growth and atresia, with a special focus on their regulation by granulosa cells. First, ovarian folliculogenesis in adult life is outlined. Then, we explain about the regulation of follicular growth and atresia by granulosa cells, in which hormones, growth factors and cytokines, death ligand-receptor system and B cell lymphoma/leukemia 2 (BCL2) family members (mitochondriamediated apoptosis) are further discussed. O varian follicle development is a process regulated by various endocrine, paracrine and autocrine factors that act coordinately to select follicles for ovulation. The vast majority of follicles (more than 99% of all follicles) fail to reach the preovulatory stage, but instead undergo the degenerative process called atresia. After the endocrine mechanisms by a hypothalamo-pituitary-ovarian axis were elucidated, granulosa cells have been the focus of interest in numerous studies that examined the mechanisms of follicular growth and atresia. From in vivo and in vitro experiments, factors secreted from granulosa cells, including gonadal steroids, growth factors, and cytokines, were shown to be essential for the survival of granulosa cells and their eventual follicular growth. Moreover, granulosa cells were observed as initial cell populations that underwent apoptosis in atretic follicles earlier than oocytes and theca cells, suggesting their role as the initiator of follicular atresia. Factors so far associated with apoptosis expressed in granulosa cells were shown to be crucial for the precise regulation of follicular growth and atresia. Here, we provide an overview of ovarian folliculogenesis in adult life and then discuss the intraovarian factors that govern follicular growth and atresia, with special emphasis on the precise mechanisms of granulosa cell survival and death.

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Section: Regulation Of Follicular Growth and Atresia By Granulosa Cellsmentioning

confidence: 98%

Follicular Growth and Atresia in Mammalian Ovaries: Regulation by Survival and Death of Granulosa Cells

et al. 2012

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“…Granulosa cell apoptosis is the first event in follicular atresia and is mediated by cell death ligand and receptor systems [7,[26][27][28]. However, there is insufficient information on the role of intracellular signaling molecules in granulosa cells, especially downstream of the activated caspase-8.…”

Section: Discussionmentioning

confidence: 99%

Effect of RNA Interference of BID and BAX mRNAs on Apoptosis in Granulosa Cell-derived KGN Cells

Sai

Matsuda

Goto

et al. 2012

Journal of Reproduction and Development

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Abstract. In mitochondrion-dependent type II apoptosis, BH3-interacting domain death agonist (BID) and BCL-2-associated X protein (BAX) promote death ligand and receptor-mediated cell death. In porcine ovaries, the levels of BID and BAX increase in follicular granulosa cells during atresia. In the present study, to confirm the pro-apoptotic activity of BID and BAX in granulosa cells, we examined the effect of RNA interference of BID or BAX on apoptosis using a human ovarian granulosa tumor cell line, KGN. By reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, expression of BID and BAX was detected in KGN cells. Then, we suppressed BID and BAX mRNA expression in KGN cells using small interfering RNA (siRNA). When BID or BAX was suppressed, a significant decrease in the apoptotic cell rate was noted. In granulosa-derived cells, BID and BAX showed pro-apoptotic activity. These results suggest that BID and BAX act as signal-transducing factors in mitochondrion-dependent type II apoptosis. Key words: BCL-2-associated X protein (BAX), BH3-interacting domain death agonist (BID), Mitochondrion-dependent type II apoptosis, RNA interference (RNAi) (J. Reprod. Dev. 58: [112][113][114][115][116] 2012) I n mammalian ovaries, more than 99% of follicles degenerate at various stages of follicular growth and development [1]. The degeneration is explained, at least in part, by the apoptosis of granulosa cells [2][3][4][5][6]. In porcine ovarian follicles in the early stages of atresia, characteristics typical of apoptosis are observed in scattered granulosa cells, but not in cumulus cells, oocytes or the cells of internal or external thecal layers [7]. As previously reported [8], it is considered that selective granulosa cell apoptosis is induced by death ligand and receptor systems as follows: When trimerized death ligands bind with trimerized death receptors located on the cell membrane, the receptors are activated. An adaptor protein (Fasassociated death domain protein) binds with activated receptors to construct death-inducing signal complex (DISC), which binds procaspase-8. Then, procaspase-8 is truncated and activated in DISC. Two types of cell death ligand and receptor-dependent signaling pathways, type I and II, have been found. Granulosa cells undergo mitochondrion-dependent type II apoptosis. Activated caspase-8 shortens BH3-interacting domain death agonist (BID) protein [9,10], and the truncated-BID (tBID) stimulates BCL-2-associated X protein (BAX). Then, BAX is transferred to the outer membrane of the mitochondrion and releases cytochrome c [11,12]. Cytochrome c binds with apoptotic protease-activating factor 1 and procaspase-9, and this complex is called an apoptosome [13]. The procaspase-9 is activated in the apoptosome and shortens procaspase-3, and the activated caspase-3 truncates caspase-3-activated DNase (CAD) [14,15]. The shortened CAD moves into the nucleus and cuts the genomic DNA leading to apoptosis.A large amount of caspase-8 is activated in type I apoptosis, but a small amo...

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“…Apoptosis is recognized as a hallmark and contributing factor of atresia of antral follicles (Tilly et al, 1991;Tilly, 1996;Chun & Hsueh, 1998;Johnson, 2003;Matsuda-Minehata et al, 2006;Inoue et al, 2011). It is a cell-specific mechanism of discrete elimination of cells during follicular atresia that ensures regression of the follicle without inciting an overt inflammatory response.…”

Section: Apoptosis As a Mechanism Of Follicular Atresiamentioning

confidence: 99%

Ovarian Follicular Atresia

Townson¹,

Combelles²

2012

Basic Gynecology - Some Related Issues

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Role of Cell-Death Ligand-Receptor System of Granulosa Cells in Selective Follicular Atresia in Porcine Ovary

Cited by 72 publications

References 59 publications

Follicular Growth and Atresia in Mammalian Ovaries: Regulation by Survival and Death of Granulosa Cells

Follicular Growth and Atresia in Mammalian Ovaries: Regulation by Survival and Death of Granulosa Cells

Effect of RNA Interference of BID and BAX mRNAs on Apoptosis in Granulosa Cell-derived KGN Cells

Ovarian Follicular Atresia

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