Apoptosis of cultured mouse luteal cells induced by tumor necrosis factor‐α and interferon‐γ

Jo, Takeo; Tomiyama, Tatsuhiro; Ohashi, Kazutomo; Saji, Fumitaka; Takahashi, Osamu; Ozaki, Masami; Yamamoto, Reiko; Yamamoto, Takashi; Nishizawa, Yasuko; Terada, Nobuyuki

doi:10.1002/ar.1092410110

Cited by 45 publications

(27 citation statements)

References 25 publications

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“…Moreover, PGF2α-induced steroid reduction results in the activation of inflammatory cells followed by TNFα and interferon-γ (IFNγ) secretion in the CL of cows [49], pigs [50], and rabbits [51]. TNFα in combination w ith IFNγ reduces P4 production and the num ber of via ble cells , although TNFα alone shows little, if any, effect [33,52]. Although, to date, there are no known studies demonstrating that IFNγ is present in the CL at the protein level, IFNγ mRNA has been detected in bovine luteal tissue collected at the end of the luteal phase of a naturally regressing CL and after induced luteolysis [49].…”

Section: Tnfα In Luteolysismentioning

confidence: 99%

“…Although, to date, there are no known studies demonstrating that IFNγ is present in the CL at the protein level, IFNγ mRNA has been detected in bovine luteal tissue collected at the end of the luteal phase of a naturally regressing CL and after induced luteolysis [49]. Treatment with IFNγ alone can decrease the P4 level and induce apoptosis [52]. Realistically, however, it is likely that TNFα works only in conjunction with IFNγ or other substances (e.g., ET-1 etc.)…”

Section: Tnfα In Luteolysismentioning

confidence: 99%

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Possible Actions of Tumor Necrosis Factor-.ALPHA. in Ovarian Function

Sakumoto

Okuda

2004

J. Reprod. Dev.

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Abstract. Tumor necrosis factor-α (TNFα) is a multifunctional cytokine that was first described as a tumoricidal factor produced by activated macrophages. Extensive research over the last two decades has suggested that TNFα has physiologically diverse actions in ovarian function in a variety of species. TNFα and its specific receptors are present in the ovaries of many species. Furthermore, TNFα plays multiple and probably important roles in corpus luteum (CL) function as well as ovarian cell function throughout the estrous cycle. This review focuses on recent studies documenting TNFα in ovarian follicles and CL in several mammals. In addition, possible roles of TNF α in ovarian function throughout the estrous cycle and in the gestation period are discussed.

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Section: Tnfα In Luteolysismentioning

confidence: 99%

Section: Tnfα In Luteolysismentioning

confidence: 99%

Possible Actions of Tumor Necrosis Factor-.ALPHA. in Ovarian Function

Sakumoto

Okuda

2004

J. Reprod. Dev.

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“…In the most well understood case, the loss of Rb is associated with loss of MHC class II inducibility in cell lines in culture (37) and in Rb-defective mice (38). The loss of functional IFN-␥ signaling could impact on tumor Ag presentation through loss of MHC class II inducibility, leading to a reduced antitumor immune response (19,36,39,40), or on the susceptibility of tumor cells to undergo apoptosis (41)(42)(43). There has also been an indication that human tumor mutations lead to a loss of IRF-2 function, which would lead to an impaired CIITA response to IFN-␥ (18,44).…”

Section: Transient Stat1 Activation and Tumorigenesismentioning

confidence: 99%

High Level Class IItrans-Activator Induction Does Not Occur with Transient Activation of the IFN-γ Signaling Pathway

Eason¹,

Blanck

2001

The Journal of Immunology

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Gene activation in early development is highly dependent on precise concentrations of trans-acting factors for the activation of different genes at differing points in the embryo. Thus, not only is the presence or absence of a particular trans-activator or repressor relevant in determining gene activation, but also the concentration of the regulatory protein must be above or below a certain threshold for proper gene regulation. Signaling pathways in somatic cells are thought to represent cascades of on/off switches, mediated most commonly by phosphorylation. Here we demonstrate a quantitative mechanism for regulating the level of a component of the IFN-γ signaling pathway that in effect represents the differential sensitivities of STAT1, IFN-regulatory factor-1, and class II trans-activator (CIITA) to IFN-γ. Unlike developmental gene regulation, in which specificity of gene activation is a function of regulatory protein concentrations, specificity of gene activation in the IFN-γ signaling pathway is regulated by the duration of the activation of the primary IFN-γ-regulatory protein, STAT1. This result most likely explains previously reported data indicating that a minimum amount of IFN-γ is required for MHC class II gene activation despite the fact that the level of the IFN-γ-inducible factor directly required for MHC class II induction, CIITA, directly correlates with the level of MHC class II expression. The induction of a high level of CIITA is dependent on sustained IFN-γ signaling. The possible implications of this result for tumorigenesis are discussed.

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“…In spite of having several hundred thousands of follicles in the mammalian ovary being in primordial and primary stages of development, only very few of them in each cycle become fully mature, while others are eliminated by atresia, a process that exhibits both the biochemical and the morphological features of programmed cell death (18). Moreover, in each reproductive cycle, a new corpus luteum is formed while the old one degenerate in a process called luteolysis, which is by nature an apoptotic process (14).…”

Section: The Cultivation Of Human Granulosa Cellsmentioning

confidence: 99%

The Cultivation of Human Granulosa Cells

Brůčková

Soukup

Moos

et al. 2008

Acta Med. (Hradec Kralove, Czech Repub.)

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Summary:The major functions of granulosa cells (GCs) include the production of steroids, as well as a myriad of growth factors to interact with the oocyte during its development within the ovarian follicle. Also FSH stimulates GCs to convert androgens (coming from the thecal cells) to estradiol by aromatase. However, after ovulation the GCs produce progesterone that may maintain a potential pregnancy. Experiments with human GCs are mainly focused on the purification of GCs from ovarian follicular fluid followed by FACS analysis or short-term cultivation. The aim of our study was to cultivate GCs for a long period, to characterize their morphology and phenotype. Moreover, we have cultivated GCs under gonadotropin stimulation in order to simulate different pathological mechanisms during folliculogenesis (e.g. ovarian hyperstimulation syndrome). GCs were harvested from women undergoing in vitro fertilization. Complex oocyte-cumulus oophorus was dissociated by hyaluronidase. The best condition for transport of GCs was optimized as short transport in follicular fluid at 37 °C. GCs expansion medium consisted of DMEM/F12, 2 % FCS, ascorbic acid, dexamethasone, L-glutamine, gentamycine, penicillin, streptomycin and growth factors (EGF, bFGF). GCs transported in follicular fluid and cultivated in 2 % FCS containing DMEM/F12 medium supplemented with follicular fluid presented increased adhesion, proliferation, viability and decreased doubling time. Cell viability was 92 % and mean cell doubling time was 52 hrs. We have optimized transport and cultivation protocols for long-term cultivation of GCs.

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Apoptosis of cultured mouse luteal cells induced by tumor necrosis factor‐α and interferon‐γ

Abstract: The presence of IFN-gamma modulates the ability of TNF-alpha to induce a reduction in the number of viable cells, although TNF-alpha alone at high concentrations can induce a reduction in the number of viable cells.

Cited by 45 publications

References 25 publications

Possible Actions of Tumor Necrosis Factor-.ALPHA. in Ovarian Function

Possible Actions of Tumor Necrosis Factor-.ALPHA. in Ovarian Function

High Level Class IItrans-Activator Induction Does Not Occur with Transient Activation of the IFN-γ Signaling Pathway

The Cultivation of Human Granulosa Cells

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