TRAIL pathway components and their putative role in granulosa cell apoptosis in the human ovary

Jääskeläinen, Minna; Kyrönlahti, Antti; Anttonen, Mikko; Nishi, Yoshihiro; Yanase, Toshihiko; Secchiero, Paola; Zauli, Giorgio; Tapanainen, Juha S.; Heikinheimo, Markku; Vaskivuo, Tommi

doi:10.1016/j.diff.2008.12.001

Cited by 21 publications

(22 citation statements)

References 37 publications

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“…In the adult human ovary, mRNA of TRAIL and its receptors, DR4, DR5, DcR1 and DcR2, was expressed in granulosa cells and oocytes. TRAIL efficiently induced apoptosis in KGN cells [58]. TRAIL may regulate directly or indirectly the apoptosis of granulosa cells.…”

Section: Trail and Trailrs In Granulosa Cell Apoptosismentioning

confidence: 86%

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

et al. 2011

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Abstract. In the mammalian ovary, more than 99% of follicles degenerate without ovulation and few oocytes ovulate and succeed to the next generation. Granulosa cell apoptosis plays a critical role in this process, follicular atresia. However, the molecular mechanisms responsible for the regulation of granulosa cell apoptosis have not been clarified. Death ligand and receptor systems are major apoptosis-inducing factors. This review describes the granulosa cell apoptosis via death ligand and receptor systems during follicular atresia in the porcine ovary.

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Section: Trail and Trailrs In Granulosa Cell Apoptosismentioning

confidence: 86%

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

et al. 2011

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“…Adult human ovaries expressed TRAIL, DR5, DcR1 and DcR2 in the granulosa cells and oocytes of small primary/secondary follicles as well as in granulosa and theca cells of antral follicles. In a human granulosa cell tumorderived cell line, TRAIL efficiently induced apoptosis, which was blocked by a caspase inhibitor [82]. The expression level of TRAIL increases during atresia, whereas that of its receptor, DR4, shows no change in the granulosa cells of pig antral follicles [83].…”

Section: Tnf-α-related Apoptosis-inducing Ligand (Trail)mentioning

confidence: 99%

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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“…In situ hybridization and immunohistochemical analysis has also shown TRAIL and its receptors to be expressed in adult human granulosa cells at multiple stages of folliculogenesis (325). Immunohistochemical analysis of a tissue microarray containing 80 primary and 12 recurrent GCT samples showed DR4 expression to be strong or intermediate in 18 and 73% of samples, respectively, with only 9% exhibiting low DR4 expression levels (326).…”

Section: G Apoptosismentioning

confidence: 99%

Molecular Pathogenesis of Granulosa Cell Tumors of the Ovary

2012

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Granulosa cell tumors of the ovary (GCT) comprise a distinct subset of ovarian cancers that account for approximately 5% of all ovarian malignancies. They are thought to arise from normal proliferating granulosa cells of the late preovulatory follicle and exhibit many morphological and biochemical features of these cells. GCT are distinct from other ovarian carcinomas in their hormonal activity; their ability to secrete estrogen, inhibin, and Müllerian inhibiting substance accounts for some of the clinical manifestations of the disease and also provides useful tumor markers for disease surveillance. Although considered to be of low malignant potential, GCT are commonly associated with slow, indolent disease progression, and frequent yet long delays to tumor recurrence are characteristic of this disease. Unlike the more intensely investigated epithelial ovarian tumors, relatively little is known about the molecular and genetic changes that give rise to GCT. To date, many investigations have centered around pathways known to be involved in normal granulosa cell proliferation, including those activated by FSH receptor stimulation. Most recently, the finding that approximately 97% of adult GCT harbor a somatic missense mutation in the FOXL2 gene (c.402C→G; p.C134W) represents an exciting advancement in the field of GCT research. The high frequency with which the mutation occurs in adult GCT, along with its absence from juvenile GCT and other human malignancies is suggestive of an oncogenic or gain-of-function mutation and, indeed, that the mutation is pathognomonic for adult GCT. In this review, we explore the implications of this finding and the most recent work characterizing molecular pathways of potential pathogenetic significance in GCT.

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TRAIL pathway components and their putative role in granulosa cell apoptosis in the human ovary

Cited by 21 publications

References 37 publications

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

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

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

Molecular Pathogenesis of Granulosa Cell Tumors of the Ovary

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