Altered expression of Fas/Fas ligand/caspase 8 and membrane type 1-matrix metalloproteinase in atretic follicles within dehydroepiandrosterone-induced polycystic ovaries in rats

Abstract

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.

Effects of dietary protein levels on the disease resistance, immune function and physical barrier function in the gill of grass carp ( Ctenopharyngodon idella ) after challenged with Flavobacterium columnare

“…In humans, the two primary pathways to initiate apoptosis are the death receptor pathway and the mitochondrial pathway [86]. The death receptor pathway is primarily regulated by FasL and caspase 8 in rats [87], and the inhibition of FasL can decrease caspase 8 activity in Jurkat T lymphocytes [88]. In our study, compared with low or high levels of protein, at an optimal level of dietary protein, the mRNA level of FasL was down-regulated in the gills of grass carp.…”

Changes in the Expression of Decoy Receptor 3 in Granulosa Cells During Follicular Atresia in Porcine Ovaries

“…FasL and Fas has also been considered to participate in apoptosis during follicular atresia in the mammalian ovary, based on their expression in ovarian follicles [27,[33][34][35][36][37][38][39][40][41][42] and pro-apoptotic activities of FasL and antibodies to Fas in follicular cells. Increases in the expression of either or both of Fas and FasL have been observed during follicular atresia in mice [36], rats [37,42], cattle [43] and pigs [27].…”

“…Increases in the expression of either or both of Fas and FasL have been observed during follicular atresia in mice [36], rats [37,42], cattle [43] and pigs [27]. It has been reported that FasL was expressed in porcine granulosa cells and that its expression level and the percentage of apoptotic cells were increased by the effect of haem oxygenase, whose expression was increased in atretic follicles [44].…”

“…TNF-related apoptosis-inducing ligand (TRAIL) and its receptors, death receptor-4 (DR4), death receptor-5 (DR5) and decoy receptor-1 (DcR1), were expressed in porcine granulosa cells [29][30][31], and expression of DcR1 is reduced in granulosa cells in atretic follicles [31]. In addition, removal of DcR1 from the cellular surface sensitizes granulosa cells to TRAIL induced-apoptosis in vitro [30].FasL and Fas has also been considered to participate in apoptosis during follicular atresia in the mammalian ovary, based on their expression in ovarian follicles [27,[33][34][35][36][37][38][39][40][41][42] and pro-apoptotic activities of FasL and antibodies to Fas in follicular cells. Increases in Fig.…”

Disrupted hyaluronan binding protein 1 (HABP1) expression: one of the key mediator for ovarian dysfunction in polycystic ovary rat

“…Several evidences are documented previously, suggesting that abnormal follicular physiology in PCO may be resulted due to disrupted ovarian tissue remodeling machinery. For instance, PCO is associated with irregular folliculogenesis and extracellular matrix (ECM) modifications along with up-regulation/hyperactivation of MMPs [MMP9 (matrix metalloproteinase-9), MMP2 (matrix metalloproteinase-2) and MT1-MMP (Membrane type 1-matrix metalloproteinase)] [3][4][5] that normally facilitate the degradation of basal lamina to breach the apical ovarian surface epithelium during ovulation. Moreover, normal follicles show HA (hyaluronan) and hyaluronan binding proteins [called as ''hyaladherins'' e.g., TSG-6 (TNF-a-stimulated gene/protein 6), PTX-3 (Pentraxin-3)] coordinated COC (cumulus-oocyte complex) expansion before successful ovulation [6,7], which is missing in PCO.…”