Prostaglandin F2 Alpha Triggers the Disruption of Cell Adhesion with Cytokeratin and Vimentin in Bovine Luteal Theca Cells.
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ABSTRACT:
SUBMITTER: Lee SH
PROVIDER: S-EPMC8069824 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Prostaglandin F2? (PGF2?) has been proposed as a functional luteolysin in primates. However, administration of PGF2? or prostaglandin synthesis inhibitors in vivo both initiate luteolysis. These contradictory findings may reflect changes in PGF2? receptors (PTGFRs) or responsiveness to PGF2? at a critical point during the life span of the corpus luteum. The current study addressed this question using ovarian cells and tissues from female cynomolgus monkeys and luteinizing granulosa cells from healthy women undergoing follicle aspiration. PTGFRs were present in the cytoplasm of monkey granulosa cells, while PTGFRs were localized in the perinuclear region of large, granulosa-derived monkey luteal cells by mid-late luteal phase. A PTGFR agonist decreased progesterone production in luteal cells obtained at mid-late and late luteal phases, but did not decrease progesterone production by granulosa cells or luteal cells from younger corpora lutea. These findings are consistent with a role for perinuclear PTGFRs in functional luteolysis. This concept was explored using human luteinizing granulosa cells maintained in vitro as a model for luteal cell differentiation. In these cells, PTGFRs relocated from the cytoplasm to the perinuclear area in an estrogen- and estrogen receptor-dependent manner. Similar to our findings with monkey luteal cells, human luteinizing granulosa cells with perinuclear PTGFRs responded to a PTGFR agonist with decreased progesterone production. These data support the concept that PTGFR stimulation promotes functional luteolysis only when PTGFRs are located in the perinuclear region. Estrogen receptor-mediated relocation of PTGFRs within luteal cells may be a necessary step in the initiation of luteolysis in primates.
| S-EPMC4380810 | biostudies-literature
Project description:In several species including the buffalo cow, prostaglandin (PG) F2? is the key molecule responsible for regression of corpus luteum (CL). Experiments were carried out to characterize gene expression changes in the CL tissue at various time points after administration of luteolytic dose of PGF2? in buffalo cows. Circulating progesterone levels decreased within 1 h of PGF2? treatment and evidence of apoptosis was demonstrable at 18 h post treatment. Microarray analysis indicated expression changes in several of immediate early genes and transcription factors within 3 h of treatment. Also, changes in expression of genes associated with cell to cell signaling, cytokine signaling, steroidogenesis, PG synthesis and apoptosis were observed. Analysis of various components of LH/CGR signaling in CL tissues indicated decreased LH/CGR protein expression, pCREB levels and PKA activity post PGF2? treatment. The novel finding of this study is the down regulation of CYP19A1 gene expression accompanied by decrease in expression of E2 receptors and circulating and intra luteal E2 post PGF2? treatment. Mining of microarray data revealed several differentially expressed E2 responsive genes. Since CYP19A1 gene expression is low in the bovine CL, mining of microarray data of PGF2?-treated macaques, the species with high luteal CYP19A1 expression, showed good correlation between differentially expressed E2 responsive genes between both the species. Taken together, the results of this study suggest that PGF2? interferes with luteotrophic signaling, impairs intra-luteal E2 levels and regulates various signaling pathways before the effects on structural luteolysis are manifest.
| S-EPMC4125180 | biostudies-literature
Project description:Luteinizing hormone (LH) regulates several ovarian functions. However, the luteoprotective mechanisms of LH involved in the maintenance of bovine corpus luteum (CL) function are not well understood. Since prostaglandin F2? (PGF), PGE2 and progesterone (P4) are well documented as antiapoptotic factors in the bovine CL, we hypothesized that LH protects the CL by stimulating the local production and action of PGF, PGE2 and P4. Cultured bovine luteal cells obtained at the mid-luteal stage (days 8-12 of the estrous cycle) were treated with LH (10 ng/ml), onapristone (OP: a specific P4 receptor antagonist, 100 ?M) and indomethacin [INDO; a cyclooxygenase (COX) inhibitor, 100 ?M] for 24 h. LH with and without OP significantly increased the mRNA and protein expressions of COX-2, PGF synthase and carbonyl reductase (P<0.05) but not the mRNA and protein expressions of COX-1 and PGE synthase in bovine luteal cells. In addition, these treatments significantly increased PGF and P4 production (P<0.05) but not PGE2 production. Luteal cell viability was significantly increased by LH alone (P<0.05), but LH-increased cell viability was reduced by LH in combination with INDO as well as OP (P<0.05). The overall results suggest that LH prevents luteal cell death by stimulating luteal PGF and P4 production and supports CL function during the luteal phase in cattle.
| S-EPMC3934132 | biostudies-literature
Project description:BackgroundPGF2? is essential for the induction of the corpus luteum regression which in turn reduces progesterone production. Early growth response (EGR) proteins are Cys2-His2-type zinc-finger transcription factor that are strongly linked to cellular proliferation, survival and apoptosis. Rapid elevation of EGR1 was observed after luteolytic dose of PGF2?. EGR1 is involved in the transactivation of many genes, including TGF?1, which plays an important role during luteal regression.MethodsThe current study was conducted in buffalo luteal cells with the aim to better understand the role of EGR1 in transactivation of TGF?1 during PGF2? induced luteal regression. Luteal cells from mid stage corpus luteum of buffalo were cultured and treated with different doses of PGF2? for different time durations. Relative expression of mRNAs encoding for enzymes within the progesterone biosynthetic pathway (3?HSD, CYP11A1 and StAR); Caspase 3; AKT were analyzed to confirm the occurrence of luteolytic event. To determine if EGR1 is involved in the PGF2? induced luteal regression via induction of TGF?1 expression, we knocked out the EGR1 gene by using CRISPR/Cas9.ResultThe present experiment determined whether EGR1 protein expression in luteal cells was responsive to PGF2? treatment. Quantification of EGR1 and TGF?1 mRNA showed significant up regulation in luteal cells of buffalo at 12 h post PGF2? induction. In order to validate the role of PGF2? on stimulating the expression of TGF?1 by an EGR1 dependent mechanism we knocked out EGR1. The EGR1 ablated luteal cells were stimulated with PGF2? and it was observed that EGR1 KO did not modulate the PGF2? induced expression of TGF?1. In PGF2? treated EGR1 KO luteal cell, the mRNA expression of Caspase 3 was significantly increased compared to PGF2? treated wild type luteal cells maintained for 12 h. We also studied the influence of EGR1 on steroidogenesis. The EGR1 KO luteal cells with PGF2? treatment showed no substantial difference either in the progesterone concentration or in StAR mRNA expression with PGF2?-treated wild type luteal cells.ConclusionThese results suggest that EGR1 signaling is not the only factor which plays a role in the regulation of PGF2? induced TGF?1 signaling for luteolysis.
| S-EPMC7953609 | biostudies-literature
Project description:Oviductal glycoprotein 1 (OVGP1), an oviductin, is involved in the maintenance of sperm viability and motility and contributes to sperm capacitation in the oviduct. In this study, the regulatory effects exerted by prostaglandin E2 (PGE2) and F2? (PGF2?) on OVGP1 expression via their corresponding receptors in bovine oviductal epithelial cells (BOECs) were investigated. BOECs were cultured in vitro, and their expression of receptors of PGE2 (PTGER1, PTGER2, PTGER3, and PTGER4) and PGF2? (PTGFR) was measured using RT-qPCR. Ca2+ concentration was determined with a fluorescence-based method and cAMP was quantified by enzyme-linked immunosorbent assays to verify activation of PTGER2 and PTGFR by their corresponding agonists in these cells. OVGP1 mRNA and protein expression was measured using RT-qPCR and western blotting, respectively, following PTGER2 and PTGFR agonist-induced activation. PTGER1, PTGER2, PTGER4, and PTGFR were found to be present in BOECs; however, PTGER3 expression was not detected. OVGP1 expression was significantly promoted by 10-6 M butaprost (a PTGER2 agonist) and decreased by 10-6 M fluprostenol (a PTGFR agonist). In addition, 3 ?M H-89 (a PKA inhibitor) and 3 ?M U0126 (an ERK inhibitor) effectively inhibited PGE2-induced upregulation of OVGP1, and 5 ?M chelerythrine chloride (a PKC inhibitor) and 3 ?M U0126 negated OVGP1 downregulation by PGF2?. In conclusion, this study demonstrates that OVGP1 expression in BOECs is enhanced by PGE2 via PTGER2-cAMP-PKA signaling, and reduced by PGF2? through the PTGFR-Ca2+-PKC pathway.
| S-EPMC5902897 | biostudies-literature
Project description:In ruminants, prostaglandin F2alpha (PGF2?)-mediated luteolysis is essential prior to estrous cycle resumption, and is a target for improving fertility. To deduce early PGF2?-provoked changes in the corpus luteum a short time-course (0.5-4 h) was performed on cows at midcycle. A microarray-determined transcriptome was established and examined by bioinformatic pathway analysis. Classic PGF2? effects were evident by changes in early response genes (FOS, JUN, ATF3) and prediction of active pathways (PKC, MAPK). Several cytokine transcripts were elevated and NF-?B and STAT activation were predicted by pathway analysis. Self-organizing map analysis grouped differentially expressed transcripts into ten mRNA expression patterns indicative of temporal signaling cascades. Comparison with two analogous datasets revealed a conserved group of 124 transcripts similarly altered by PGF2? treatment, which both, directly and indirectly, indicated cytokine activation. Elevated levels of cytokine transcripts after PGF2? and predicted activation of cytokine pathways implicate inflammatory reactions early in PGF2?-mediated luteolysis.
| S-EPMC7388008 | biostudies-literature
Project description:We recently demonstrated that luteal cells flow out from the ovary via lymphatic vessels during luteolysis. However, the regulatory mechanisms of the outflow of luteal cells are not known. Matrix metalloproteinases (MMPs) can degrade the extracellular matrix and basal membrane, and tissue inhibitors of matrix metalloproteinases (TIMPs) inhibit the activity of MMPs. To test the hypothesis that MMP expression in luteal cells is regulated by luteolytic factors, we investigated the effects of prostaglandin F2α (PGF), interferon γ (IFNG) and tumor necrosis factor α (TNF) on the mRNA expression of MMPs and TIMPs in cultured luteal cells. Luteal cells obtained from the CL at the mid-luteal stage (days 8-12 after ovulation) were cultured with PGF (0.01, 0.1, 1 μM), IFNG (0.05, 0.5, 5 nM) and TNF (0.05, 0.5, 0.5 nM) alone or in combination for 24 h. PGF and IFNG significantly increased the expression of MMP-1 mRNA. In addition, 1 μM PGF in combination with 5 nM IFNG stimulated MMP-1 and MMP-9 mRNA expression significantly more than either treatment alone. In contrast, IFNG significantly decreased the level of MMP-14 mRNA. The mRNA expression of TIMP-1, which preferentially inhibits MMP-1, was suppressed by 5 nM INFG. One μM PGF and 5 nM IFNG suppressed TIMP-2 mRNA expression. These results suggest a new role of MMPs: luteal MMPs stimulated by PGF and IFNG break down the extracellular matrix surrounding luteal cells, which accelerates detachment from the CL during luteolysis, providing an essential prerequisite for outflow of luteal cells from the CL to lymphatic vessels.
| S-EPMC4547985 | biostudies-literature
Project description:BACKGROUND:Prostaglandin F2? (PGF2?) is an important component for the physiology of female reproductive processes. In the literature, the data pertaining to the synthesis and action of PGF2? in early embryonic bovine development are limited. In our study, we used the bovine in vitro culture model based on the time of first cleavage to determine the mRNA expression and immunolocalization of PGF2? synthase and its receptor in bovine embryos from the 2-cell stage to the hatched blastocyst stage. We also evaluated PGF2? production at 2, 5 and 7?days of in vitro culture. RESULTS:We found a significantly higher proportion of blastocysts obtained from the early-cleaved embryos than from the late-cleaved embryos (37.7% vs. 26.1% respectively, P?<?0.05). The PGFS mRNA expression was significantly higher in the late-cleaved group than in the early-cleaved group at the 2-, 4- and 16-cell stages (P?<?0.05). For PTGFR, we observed that within the late-cleaved group, the mRNA abundance was significantly higher in embryos at the 2- and 16-cell stages than in embryos at the 4- and 8-cell stages (P?<?0.05). We observed that PTGFR mRNA expression was significantly higher in the 2- and 16-cell embryos in the late-cleaved group than that in the early-cleaved group embryos (P?<?0.05). Among the blastocysts, the PGFS and PTGFR expression levels showed a trend towards higher mRNA expression in the late-cleaved group than in the early-cleaved group. Analysis of PGF2? production showed that within the early-cleaved group, the content of PGF2? in the in vitro culture medium was significantly higher on day 7 than it was on day 2 (P?<?0.05). CONCLUSIONS:The mRNA expression levels of PGF2? synthase and its receptor depend on the developmental stage and the embryo quality. Analyses of PGFS and PTGFR expression in bovine blastocysts and of PGF2? embryo production suggest that prostaglandin F2? can act in an autocrine and paracrine manner in bovine in vitro-produced preimplantation embryos. Moreover, the tendency of PTGFR and PGFS mRNA expression to be upregulated in embryos with low developmental potential can indicate a compensation mechanism related to high PGFS and PTGFR mRNA expression levels in low-quality embryos.
| S-EPMC6570898 | biostudies-literature
Project description:Cortisol (Cr), the most important glucocorticoid (GC), is well known to suppress uterine prostaglandin F2? (PGF) production. However, the details of the regulatory mechanisms controlling the cyclic changes in endometrial PGF production remain unclear. Here we investigated the expression of the GC receptor (GC-R?), the actions of cortisol throughout the estrous cycle and the regulatory mechanism of GC-R? in the bovine endometrium. The levels of GC-R? protein were greater at the mid-luteal stage (Days 8-12) than at the other stages. Cr more strongly suppressed PGF production at the mid-luteal stage than at the follicular stage. GC-R? expression was increased by progesterone (P4) but decreased by estradiol-17? (E2) in cultured endometrial stromal cells. The overall results suggest that ovarian steroid hormones control the cyclic changes in endometrial PGF production by regulating GC-R? expression in bovine endometrial stromal cells.
| S-EPMC3944365 | biostudies-literature
Project description:In the present study, the question was addressed whether the feline placenta can synthesize prostaglandin F2? (PGF2?). The PGFS protein was elevated, particularly at 2.5-3 weeks of pregnancy compared to 7-8 (P < 0.05) and 8.5-9 weeks (P < 0.001). Transcripts for PGFS were significantly upregulated at 2.5-3 weeks of pregnancy and then gradually declined towards the end of gestation (P < 0.001). Transcripts for PTGS2 were only upregulated in placentas from queens close to term (P < 0.001) compared with earlier phases. Staining of PTGS2 showed distinct positive signals in placentas obtained during the last week before labor, particularly in the strongly invading trophoblast surrounding blood vessels, and also in decidual cells. Shortly after implantation, signals for PGFS were localized in the trophoblast cells. Near term, PGFS staining was seen mainly in decidual cells. Both placental PGF2? and plasma PGFM were elevated towards the end of pregnancy (P < 0.001) compared with earlier weeks of pregnancy. The content of PGF2? in extracted placenta mirrored the PGFM level in plasma of pregnant females. During late gestation there is a significant increase in PGFM levels in maternal blood and of PGF2? levels in placental tissue concomitant with an upregulation of placental PTGS2.
| S-EPMC3934528 | biostudies-literature