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Altered expression of Fas/Fas ligand/caspase 8 and membrane type 1-matrix metalloproteinase in atretic follicles within dehydroepiandrosterone-induced polycystic ovaries in rats. Honnma H et al. One of the characteristics of polycystic ovary syndrome (PCOS) is the presence of cystic follicles in various stages of growth and atresia, the latter of which is known to be the result of apoptosis and tissue remodeling. To further investigate the process of follicular atresia, we compared ovarian expression and localization of Fas, Fas ligand (FasL), casapse-8 and membrane-type1 matrix metalloproteinase (MT1-MMP) in rats treated with dehydroepiandrosterone (DHEA) as a model of PCOS, and in control rats. We found that the numbers of TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive follicles were significantly higher in ovaries from PCOS rats than in those from control rats (P < 0.05), as were ovarian levels of FasL mRNA and protein, processed caspase-8 protein and MT1-MMP mRNA. Correspondingly, we also observed an increase in the level of MTI-MMP catalytic activity and a decrease in the level of pro-caspase-8 protein. In addition, immunohistochemical analyses showed that MT1-MMP and FasL co-localize with TUNEL-positive apoptotic granulosa cells within atretic follicles of PCOS ovaries. Our results suggest that under the PCOS-like conditions induced by DHEA, the Fas/FasL/Caspase-8 (death receptor dependent) pathway is pivotal for follicular atresia, and that increased levels of MT1-MMP likely play an important role in tissue remodeling during structural luteolysis.
Gene whose expression is detected by cDNA array hybridization: GDP/GTP exchangers, GTPase stimulators and inhibitors, apoptosis Rozenn Dalbi?Tran and Pascal Mermilloda
Activity and expression of different members of the caspase family in the rat corpus luteum (CL) during pregnancy and postpartum. Peluffo MC et al. Studies were designed to examine the expression and activity of four caspases, which contribute to the initial (caspases-2, -8 and -9) and final (caspase-3) events in apoptosis, in the rat CL during pregnancy (days, 7, 17, 19 and 21 of gestation), postpartum (day 1 and 4) and after injection (0, 8, 16, 24 and 36 h) of the physiological luteolysin, PGF-2alpha. In addition, the temporal relationship of caspase expression/activity relative to steroid production and luteal regression was evaluated. During pregnancy, the activity of all four caspases was significantly greater on day 19, prior to a decline in CL progesterone (P) and CYP11A1 levels at day 21 of gestation. The levels of the caspase-3 active fragment (p17, measured by Western blot) also increased at day 19 and 21 of pregnancy. Immunohistochemical analyses detected specific staining for the caspases in luteal cells (large and small), as well as, in endothelial cells. However, the percentage of apoptotic cells did not increase in the CL until postpartum. Following PGF-2alpha injection, there was a significant decrease in CL P by 24 h, though the activity of all four caspases did not increase until 36 h post treatment. The active p17 fragment of caspase-3 also significantly increased at 36 h post- PGF-2alpha. These results suggest that an increase in the activity of caspase-2, -8, -9 and -3 is associated with the early events of natural luteolysis at the end of pregnancy. Also the exogenous administration of the luteolysin PGF-2alpha may regulate members of the caspase family. Key words: caspases, luteolysis, corpus luteum, pregnancy.
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Expression of caspase-2, -3, -8 and -9 proteins and enzyme activity in the corpus luteum of the rat at different stages during the natural estrous cycle. Peluffo MC et al. Apoptosis is associated with the regression of the corpus luteum (CL) in many species. Since caspases play a central role in apoptosis, we studied several initiators (-2, -8, and -9) and the main effector (-3) caspase in the CL during the estrous cycle of the rat. Two different populations of CL (old and new) were identified on ovaries at estrus and diestrus II (DII). Diminished (P < 0.05) luteal progesterone content and P450scc levels suggested that functional luteolysis occurred between the new CL at DII and old CL at estrus, whereas the decline (P < 0.05) in luteal weight indicated that structural regression was occurring between old CL at estrus to DII. Immunostaining for caspase-2 in luteal and endothelial cells appeared to increase as the luteal phase progressed, peaking at DII in the old CL. However, caspase-8 and -9 immunostaining showed little change with a slight increase at estrus in the old population. Notably, caspase-3 staining appeared to peak at DII in the new CL. Enzyme activity of caspase-9 increased (P < 0.05) in the new CL at DII, followed by that of caspase-2 and -3 in old CL at estrus. Caspase-8 activity did not change at any stage. The number of apoptotic cells increased at DII in the old CL. These results suggest an important role for this protease family during early events of luteolysis in the rat estrous cycle.
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