Estrous cycle dependent changes in expression and distribution of Fas, Fas ligand, Bcl-2, Bax, and pro- and active caspase-3 in the rat ovary

Slot, K.A.; Voorendt, Marsha; Boer-Brouwer, Mieke de; Vugt, H.H. van; Teerds, Katja J.

doi:10.1677/joe.1.06165

Cited by 62 publications

(68 citation statements)

References 82 publications

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“…Immunohistochemistry data demonstrate that most of these proteomic changes are evident in both LLC and SLC on day 16 of the estrous cycle or pregnancy. Previous studies clearly indicate a role for caspase-3 in luteal cell apoptosis in various species (Carambula et al 2002, Davis & Rueda 2002, Peluffo et al 2005, Yadav et al 2005, Slot et al 2006. Together, present results along with previous findings suggest that activation of caspase-3 dependent as well as independent apoptosis pathways are required for natural luteolysis; whereas, these pathways need to be inhibited or suppressed to maintain the survival of the CL during establishment of pregnancy in sheep.…”

Section: Survival and Apoptosis Proteins In The CLsupporting

confidence: 83%

“…By contrast, interactions between pro-apoptotic and anti-apoptotic signaling pathways and activation of caspases-3 dependent or independent intrinsic apoptosis pathways determine the death of cells (Adams & Cory 1998, Jiang & Wang 2004. Previous studies have shown that administration PGF 2a regulates genes or protein associated with cell survival and apoptosis in cows (Davis & Rueda 2002, Hou et al 2008, Arvisais et al 2010, Atli et al 2012, sheep (Romero et al 2013), pigs (Diaz et al 2013), rodents (Carambula et al 2002, Slot et al 2006, and primates (Peluffo et al 2005, Yadav et al 2005 during induced luteolysis in vivo and in vitro models. Although there is a large body of information available on induced luteolysis in various species, temporal regulations of cell survival and apoptosis signaling protein machinery in the CL during natural luteolysis and establishment of pregnancy in ruminants are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Early pregnancy modulates survival and apoptosis pathways in the corpus luteum in sheep

Lee¹,

Banu²,

McCracken³

et al. 2016

Reproduction

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The corpus luteum (CL) is a transient endocrine gland. Functional and structural demise of the CL allows a new estrous cycle. On the other hand, survival of CL and its secretion of progesterone are required for the establishment of pregnancy. Survival or apoptosis of the luteal cells is precisely controlled by interactions between survival and apoptosis pathways. Regulation of these cell signaling components during natural luteolysis and establishment of pregnancy is largely unknown in ruminants. The objective of the present study was to determine the regulation of survival and apoptosis signaling protein machinery in the CL on days 12, 14, and 16 of the estrous cycle and pregnancy in sheep. Results indicate that: i) expressions of p-ERK1/2, p-AKT, b-catenin, NFkB -p65, -p50, -p52, p-Src, p-b -arrestin, p-GSK3b, X-linked inhibitor of apoptosis protein (XIAP), and p-CREB proteins are suppressed during natural luteolysis; in contrast, their expressions are sustained or increased during establishment of pregnancy; ii) expressions of cleaved caspase-3, apoptosis inducing factor (AIF), c-Fos, c-Jun, and EGR-1 proteins are increased during natural luteolysis; in contrast, their expressions are decreased during establishment of pregnancy; and iii) expressions of Bcl-2, Bcl-XL, Bad, and Bax proteins are not modulated during natural luteolysis while expressions of Bcl2 and Bcl-XL proteins are increased during establishment of pregnancy in sheep. These proteomic changes are evident in both large and small luteal cells. These results together indicate that regression of the CL during natural luteolysis or survival of the CL during establishment of pregnancy is precisely controlled by distinct programmed suppression or activation of intraluteal cell survival and apoptosis pathways in sheep/ruminants.

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Section: Survival and Apoptosis Proteins In The CLsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Early pregnancy modulates survival and apoptosis pathways in the corpus luteum in sheep

Lee¹,

Banu²,

McCracken³

et al. 2016

Reproduction

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“…Bid and Bax, Bcl-2 family members, act as proapoptotic factors in the type II pathway [20][21][22][23][24][25][26][27][28][29][30][31][32][33]. These Bcl-2 family members are expressed in the cultured ovarian cells of rodents [50,51] and ovarian tissues of rodents [52,53] and ruminants [54,55]. However, it is not clear whether Bid and Bax are expressed in pig ovaries and involved in granulosa cell apoptosis in porcine follicles.…”

Section: Discussionmentioning

confidence: 99%

Bid and Bax Are Involved in Granulosa Cell Apoptosis During Follicular Atresia in Porcine Ovaries

Sai

Goto

Yoshioka

et al. 2011

Journal of Reproduction and Development

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Abstract. More than 99% of follicles undergo "atresia" during follicular development and growth. Follicular atresia is predominantly regulated by granulosa cell apoptosis. However, the intracellular signaling pathway of apoptosis in granulosa cells has not been revealed. In the present study, we examined changes in the expression of BH3-interacting domain death agonist (Bid) and Bcl-2-associated X protein (Bax), which are considered to promote the cell death ligand/ receptor-mediated process in mitochondrion-dependent type II apoptosis, in porcine granulosa cells during atresia. Levels of mRNA and protein of Bid and Bax were determined by the reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting techniques, respectively. Levels of Bid and Bax mRNA and protein were markedly increased in granulosa cells of early atretic follicles compared with those of healthy follicles. In situ hybridization and immunohistochemical staining revealed that mRNA and protein of Bid and Bax were present in the granulosa cells, though only traces were found in healthy follicles; however, strong staining was noted in atretic follicles. These results indicate that Bid and Bax appear to be signal transduction factors in granulosa cells during follicular atresia and appear to play proapoptotic roles and confirm that the porcine granulosa cell is a mitochondrion-dependent type II apoptotic cell. Key words: Bcl-2-associated X protein (Bax), BH3-interacting domain death agonist (Bid), Follicular atresia, Mitochondrion-dependent type II apoptotic cell, Pig ovary (J. Reprod. Dev. 57: [421][422][423][424][425][426][427] 2011) 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 the early stages of follicular atresia in pig ovaries, biochemical and morphological characteristics typical of apoptosis, namely nuclear fragmentation, chromatin condensation and cell shrinkage, are observed in scattered granulosa cells located on the inner surface of the follicular wall, but not in cumulus cells, oocytes or the cells of internal or external thecal layers [7,8]. However, the intracellular signal transduction pathway of apoptosis in granulosa cells of pig ovaries is not well understood.Selective apoptotic cell death is induced by cell death ligand/ receptor systems, including Fas ligand (FasL; also called Apo-1 ligand or CD95 ligand) and Fas (also called Apo-1 or CD95), tumor necrosis factor (TNF)-α and TNF receptors (TNFRs) and TNFrelated apoptosis-inducing ligand (TRAIL) and TRAIL receptors (DR4 and 5) [9][10][11]. The cell death ligand/receptor-mediated apoptotic signaling pathway is suggested to be as follows [12][13][14][15][16][17][18]: When trimerized cell death ligands bind with trimerized death receptors located on the cell membrane, the receptors are activated. An adaptor protein (Fas-associated death domain protein: FADD) binds with an activated rece...

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“…The binding between the FAS receptor (FAS/CD95), a member of the TNF family, and its ligands (FASLG) leads to the formation of a death-induced signaling complex (Krammer 1999, Slot et al 2006). The BCL2 family might be divided into two main groups, according to their proapoptotic (BAX, BAD, BIM, BclxS, and BOK) or antiapoptotic function (i.e., BCL2, BclxL, and BCL2L2) (Slot et al 2006). All of them are regulatory proteins whose actions occur at the mitochondrial level.…”

Section: R256 H H Ortega and Othersmentioning

confidence: 99%

“…The penultimate stage of cell death requires caspases (Das et al 2008). DNA repair enzymes and cytoskeletal and nuclear scaffold proteins are activated by caspase 3 (Scaffidi et al 1998, Krammer 1999, Slot et al 2006, which is required for apoptosis in follicular atresia. Granulosa cells, oocytes, and theca cells undergo apoptosis as part of atresia (Hsueh et al 1994, Markstrom et al 2002, to which early antral follicles are more sensitive (Markstrom et al 2002).…”

Section: R256 H H Ortega and Othersmentioning

confidence: 99%

Molecular aspects of bovine cystic ovarian disease pathogenesis

Ortega¹,

Marelli²,

Rey³

et al. 2015

Reproduction

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Cystic ovarian disease (COD) is one of the main causes of reproductive failure in cattle and causes severe economic loss to the dairy farm industry because it increases both days open in the post partum period and replacement rates due to infertility. This disease is the consequence of the failure of a mature follicle to ovulate at the time of ovulation in the estrous cycle. This review examines the evidence for the role of altered steroid and gonadotropin signaling systems and the proliferation/apoptosis balance in the ovary with cystic structures. This evidence suggests that changes in the expression of ovarian molecular components associated with these cellular mechanisms could play a fundamental role in the pathogenesis of COD. The evidence also shows that gonadotropin receptor expression in bovine cystic follicles is altered, which suggests that changes in the signaling system of gonadotropins could play a fundamental role in the pathogenesis of conditions characterized by altered ovulation, such as COD. Ovaries from animals with COD exhibit a disrupted steroid receptor pattern with modifications in the expression of coregulatory proteins. These changes in the pathways of endocrine action would trigger the changes in proliferation and apoptosis underlying the aberrant persistence of follicular cysts. Free Spanish abstract: A Spanish translation of this abstract is freely available at

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Estrous cycle dependent changes in expression and distribution of Fas, Fas ligand, Bcl-2, Bax, and pro- and active caspase-3 in the rat ovary

Cited by 62 publications

References 82 publications

Early pregnancy modulates survival and apoptosis pathways in the corpus luteum in sheep

Early pregnancy modulates survival and apoptosis pathways in the corpus luteum in sheep

Bid and Bax Are Involved in Granulosa Cell Apoptosis During Follicular Atresia in Porcine Ovaries

Molecular aspects of bovine cystic ovarian disease pathogenesis

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