Platelet-activating factor (PAF) has been implicated as a mediator in diverse pathologic processes, such as allergy,
asthma, septic shock, arterial thrombosis, and inflammatory processes . PAF is a phospholipid
(1-0-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) and exerts its various effects via specific cell surface receptors
that bind PAF with high affinity. Human PAF
receptor (PTAFR) is a member of the G protein-coupled family of receptors .
NCBI Summary:
PTAFR shows structural characteristics of the rhodopsin (MIM 180380) gene family and binds platelet-activating factor (PAF). PAF is a phospholipid (1-0-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) that has been implicated as a mediator in diverse pathologic processes, such as allergy, asthma, septic shock, arterial thrombosis, and inflammatory processes.[supplied by OMIM]
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Antral follicle growth, Ovulation, Steroid metabolism, Luteinization, Early embryo development
Comment
Abisogun AO, et al reported the involvement of platelet activating factor in ovulation.
Follicle rupture during ovulation is associated with inflammation-like changes.
Because platelet activating factor (PAF) participates in the inflammatory process,
the effect of a PAF-specific antagonist, BN52021, on the ovulatory response was
tested in rats. BN52021, administered locally, inhibited follicle rupture in rats
stimulated to ovulate with human chorionic gonadotropin (hCG). In addition to
suppressing rupture of the follicles, this antagonist suppressed the hCG-stimulated
increase in ovarian collagenolysis and vascular permeability. The inhibition of
ovulation of BN52021 could be reversed by simultaneous administration of PAF.
Furthermore, PAF partially reversed the blockage of ovulation by inhibitors of
eicosanoid synthesis. Collectively, these results suggest the involvement of PAF
in ovulation.
Battista PJ, et al reported the effects of platelet-activating factor and platelet-derived compounds on bovine
luteal cell progesterone production.
Rabinovici J, et al 1991 reported that
platelet-activating factor induces progesterone secretion and changes in
morphological appearance in luteinizing granulosa cells in vitro.
Effect of platelet-activating factor (PAF) on human spermatozoa-oocyte interactions Angle MJ, et al .
Actions of platelet activating factor (PAF) on gametes and embryos: clinical aspects. Pike IL et al. Platelet activating factor (PAF) is a phospholipid widespread in body tissues. Previous reviews have discussed its production by preimplantation embryos and the evidence implicating it as an autocrine mediator in aspects of gamete and embryo physiology. Human spermatozoa contain variable amounts of PAF, the amount contained depending on the source and method of preparation of the sperm. Incubation of human sperm with PAF tends to increase their forward velocity, especially in samples with slow motility. PAF treatment causes an increase in the proportion of acrosome-reacted sperm and in their ability to penetrate both zona-free hamster ova and cervical mucus. PAF has been found in human follicular fluid at ovulation. A role for PAF in ovulation has been suggested, because PAF antagonists reduce the rate of ovulation in rats. In some studies, modest improvements to mouse in vitro fertilization (IVF) rates have been achieved with PAF supplementation of media under specific conditions. Furthermore, in the rabbit and mouse, PAF antagonists have been reported to inhibit fertilization in vivo and in vitro respectively. However, addition of PAF to human IVF medium, but only at the time of insemination and fertilization, had no effect on either fertilization or pregnancy rates. Sensitive bio- and immuno-assays have shown that PAF is secreted by human embryos into their fluid milieu. PAF secretion by these zygotes during culture, although markedly variable, has been correlated with the achievement of pregnancy and pregnancy outcome. Although the secretion of PAF by the mouse embryo decreases during culture in vitro, exogenous PAF enhances embryo viability during culture. Similarly, culture of human zygotes in PAF-supplemented medium prior to embryo transfer significantly increases the chance of achieving pregnancy. Both the implantation and live-birth rates are increased in human IVF by addition of PAF to the medium.
Minhas BS, et al reported effects of platelet activating factor on mouse oocyte fertilization in vitro.
Platelet activating factor is rapidly gaining acceptance as a potent mediator in many reproductive processes. This study presents data that indicate a direct role of platelet activating factor in fertilization. Platelet activating factor was shown to significantly increase (p less than 0.001) the fertilization rate of mouse oocytes in vitro. Furthermore, CV3988, an inhibitor of platelet activating factor, was noted to significantly decrease in vitro fertilization rates at 10(-5) and 10(-4) mol/L concentrations.
The Effects of Platelet-Activating Factor on the Secretion of Interleukin-8 and Growth-Regulated Oncogene alpha in Human Immortalized Granulosa Cell Line (GC1a). Kawano Y et al. Problem To investigate the role of platelet-activating factor (PAF) in human ovulation, we studied the regulation of interleukin (IL)-8 and growth-regulated oncogene (GRO) alpha in cultured human immortalized granulosa cell line (GC1a). Method of study GC1a was cultured in serum-free medium, and incubated with carbamyl-PAF (C-PAF) and/or PAF receptor antagonist (WEB 2086). The supernatants were collected, and IL-8 and GRO alpha were measured by enzyme-linked immunosorbent assay. Results After treatment with C-PAF, the levels of IL-8 and GROalpha increased in a time-dependent manner. The levels of IL-8 and GROalpha were significantly increased after treatment with C-PAF in a dose-dependent manner. However, the levels of IL-8 and GROalpha were significantly decreased by treatment with C-PAF and with increasing concentrations of WEB 2086. Conclusion Our data indicated that IL-8 and GROalpha were regulated by C-PAF. The results suggested that PAF may play an important role in human pre-ovulatory processes involving IL-8 and GROalpha production.
Role of the platelet-activating factor and its receptor in the proliferative regulation of bovine ovarian granulosa cells. Viergutz T et al. Proliferation of granulosa cells and their withdrawal from the cell cycle may regulate follicular ovulation. Antagonists of platelet-activating factor (PAF) and its receptor (PAFr) inhibit follicle rupture. Objectives: Thus, PAF and PAFr may be involved in proliferative regulation of granulosa cells; however, expression of PAFr in these cells is unknown. Materials and Methods: The aim of this study was to investigate the presence of PAFr and the effect of PAF on proliferation of cultured bovine granulosa cells using real-time polymerase chain reaction to assay steady-state level of mRNA, immunocytochemistry to quantify PAFr protein and proliferating cell nuclear antigen protein by flow cytometry. Results: We found that granulosa cells express PAFr transcripts and protein. PAF presence did not change the concentration of PAFr mRNA or PAFr protein. Granulosa cells responded to PAF doses of 10 and 50 nm with increasing proportions of cells entering G(0)/G(1) phase, as well as a significant expansion of total cell numbers. Rise in G(0)/G(1)-phase cells was accompanied by a decline in proliferating cell nuclear antigen protein expression, and these effects could be suspended by simultaneous PAFr blockage. The results provide clear evidence for expression of PAFr in bovine granulosa cells and its functional involvement in PAF/PAFr-mediated stimulation of cell recruitment. Conclusions: PAF antagonists are suggested to disturb this regulative activity of PAF and to contribute in this way to blockage of ovulation.
Expression regulated by
Comment
Platelet-activating factor-stimulated production of reactive oxygen species in ovarian granulosa cells from periovulatory follicles. Xu J et al. The platelet-activating factor (PAF) is a proinflammatory lipid present in the fluid of ovarian Graafian follicle. Ovarian blockage of the PAF receptor (PAFr) reduces ovulations in the rat whereas underlying mechanism is poorly understood. Mural granulosa cells (MGC) were mechanically isolated from the theca interna of bovine periovulatory follicle. The mRNA abundance for PAFr, progesterone receptor and cyclooxygenase-2 were measured by real-time PCR. Cytosolic calcium (Ca(2+)) concentration was assayed by microscopy using Fura-2 AM as indicator, 8-isoprostaglandin F(2alpha) (8-isoPGF(2alpha)) by an ELISA kit. Fluorescent products arising from intracellular oxidation of hydroethidine (HE) and dihydrorhodamine (DHR) were quantified by flow cytometry. The cells expressed PAFr mRNA and PAFr protein and responded to cPAF (nonhydrolyzable form of PAF) with a pulsating increase in Ca(2+), demonstrating functional PAFr. Elevation of Ca(2+) was reversed by WEB-2086, an inverse PAFr agonist. cPAF elevated the level of 8-isoPGF(2alpha) in the medium of MGC cultured with luteinizing hormone (LH). cPAF alone had no significant influence on the oxidation of HE and DHR, or 8-isoPGF(2alpha) level. In MGC from vital periovulatory follicle, PAF and LH signaling plays an important role in regulating the production of excessive oxidants. Blockage of PAFr seems to interfere with these regulatory processes essential for ovulation. (c) 2009 International Society for Advancement of Cytometry.
Ovarian localization
Oocyte, Granulosa, Luteal cells, Stromal cells
Comment
Ontogeny of expression of a receptor for platelet-activating factor in mouse preimplantation embryos and the effects of fertilization and culture in vitro on its expression Stojanov T, et al .
Platelet-activating factor (PAF; 1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent ether phospholipid. It is one of the preimplantation embryo's autocrine growth/survival factors. It may act via a G protein-linked receptor on the embryo; however, the evidence for this is conflicting. The recent description of the intracellular form of the PAF:acetlyhydrolase enzyme as having structural homology with G proteins and Ras also suggests this as a potential intracellular receptor/transducer for PAF. This study used reverse transcription-polymerase chain reaction to examine the ontogeny of expression of the genes for these proteins in the oocyte and preimplantation-stage embryo. Transcripts for the G protein-linked PAF receptor were detected in the late 2-cell-stage embryo and in all stages from the 4-cell stage to blastocysts. They were also present in unfertilized oocytes and newly fertilized zygotes but only at relatively low levels. The incidence of expression was generally low and variable in late zygotes and early 2-cell embryos. Expression past the 2-cell stage was alpha-amanitin sensitive. The results indicated that mRNA for this receptor is a maternal transcript that was degraded during the zygote-2-cell stage. New expression of the receptor transcript required activation of the zygotic genome. Fertilization of embryos in vitro caused this transcript not to be expressed in the zygote. Culture of zygotes (irrespective of their method of fertilization) caused expression from the zygotic genome to be retarded by more than 24 h. This retardation did not occur if culture commenced at the 2-cell stage. The transcripts for the subunits of intracellular PAF:acetylhydrolase were not detected in oocytes or at any stage of embryo development examined, despite their being readily detected in control tissue. This study confirms the presence of the G protein-linked PAF receptor in the 2-cell embryo and describes for the first time its normal pattern of expression during early development. The adverse effects of in vitro fertilization (IVF) and embryo culture on the expression of this transcript may be a contributing factor for the poor viability of embryos produced in this manner. The reduced expression of PAF-receptor mRNA following IVF predicts that such embryos may have a deficiency in autocrine stimulation and also suggests that supplementation of growth media with exogenous PAF would be only partially beneficial. The effect of IVF and culture may also explain the conflicting literature.
Lash GE, et al 2001 reorted the localization and distribution of platelet activating factor receptors in the mouse ovary and oviduct during the estrous cycle and early pregnancy.
Mouse ovaries and oviducts taken during the estrous cycle and days 1, 4 and 7 post-conception (pc) were analyzed by [3H]PAF binding using frozen sections and autoradiography. For the outer epithelium of estrous and metestrous ovaries there was no significant difference in PAF binding (P>0.05); however, both stages were significantly different from proestrous (P<0.001). Ovarian stroma PAF binding was significantly higher (P<0.001) at estrous than metestrous, with no PAF binding at proestrous. Binding of PAF to estrous ovarian follicles was significantly greater than at proestrous and metestrous. At days 1 and 7 pc, all ovarian tissues had the greatest PAF binding with day 4 pc failing to bind PAF except for a significant decrease in corpora luteal binding.
Follicle stages
Preovulatory, Corpus luteum
Comment
Detection and preliminary characterization of two enzymes involved in biosynthesis of platelet-activating factor in mouse oocytes, zygotes and preimplantation embryos: dithiothreitol-insensitive cytidinediphosphocholine: 1-O-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase and acetyl-coenzyme A:1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase. Wells XE et al. The aim of this study was to determine whether the final enzymes in the two biosynthetic pathways for platelet-activating factor (PAF) (the 'de novo' and the 'membrane remodelling' pathways) are present in mouse embryos, zygotes and oocytes. The enzymes are dithiothreitol-insensitive cytidinediphosphocholine: 1-O-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (cholinephosphotransferase) in the de novo pathway and acetyl-coenzyme A:1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase (acetyltransferase) in the membrane remodelling pathway. Activity of both enzymes was detected in the unfertilized oocyte, the zygote and also in the preimplantation embryo (48, 72 and 96 h after the ovulatory injection of hCG). In both cases the activity was destroyed by boiling and increased linearly with incubation time and the concentration of embryo homogenate present, indicating that the reactions were catalysed by enzymes. The product of the reactions was confirmed as PAF using HPLC and structural analyses by enzymatic digestion. Cholinephosphotransferase required Mg2+ and was inhibited by Ca2+, while acetyltransferase required the presence of NaF (a phosphatase inhibitor). The activity of cholinephosphotransferase was similar in unfertilized oocytes and zygotes, and did not change significantly with advancing developmental stage in preimplantation embryos. Acetyltransferase had a significantly lower specific activity (0.078 +/- 0.044 fmol PAF per oocyte per min, mean +/- SEM) in unfertilized oocytes than in zygotes of corresponding age (0.358 +/- 0.097 fmol PAF per zygote per min) (P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment:Ishii S, et al
show that disruption of the PAF receptor gene in mice caused a marked reduction in systemic anaphylactic symptoms. Unexpectedly, however, the PAF receptor-deficient mice developed normally, were fertile, and remained sensitive to bacterial endotoxin. These mutant mice clearly show that PAF plays a dominant role in eliciting anaphylaxis, but that it is not essential for reproduction, brain development, or endotoxic shock.