Antagonists of embryo-derived platelet-activating factor prevent implantation of mouse embryos

Spinks, N. R.; O’Neill, Chris

doi:10.1530/jrf.0.0840089

Cited by 75 publications

(24 citation statements)

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“…Similarly, significantly inhibited the direct effects of exogenous PAF on the oxidative metabolism of lactate and glucose by 2-cell mouse embryos during culture in vitro (Ryan et ai, 1990). (Spinks & O'Neill, 1988) and the observed effect of exogenous PAF in enhancing the implantation potential of cultured embryos.…”

Section: Resultsmentioning

confidence: 89%

“…It has been suggested that embryo-derived PAF activity is necessary for successful implantation (Spinks & O'Neill, 1988) and that its site of action is at the embryonic level (Ryan et ai, 1989;Ryan et ai, 1990;Spinks et ai, 1990). In view of the reduced secretion of embryo-derived PAF after in-vitro culture (Ryan et ai, 1989), PAF may be a limiting factor in maintaining embryo viability during culture in vitro.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Implantation potential and fetal viability of mouse embryos cultured in media supplemented with platelet-activating factor

Ryan

Spinks²,

O’Neill³

et al. 1990

Reproduction

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Section: Resultsmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Implantation potential and fetal viability of mouse embryos cultured in media supplemented with platelet-activating factor

Ryan

Spinks²,

O’Neill³

et al. 1990

Reproduction

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“…1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphocholine (platelet-activating factor, PAF) was the first characterized factor released by the preimplantation embryo to be identified (O'Neill, 1985a;O'Neill, 1985b). It was subsequently shown that PAF also stimulated embryo metabolism , cell cycle progression (Roberts et al, 1993) and embryo viability Spinks and O'Neill, 1988;Spinks et al, 1990), thereby providing evidence for an autocrine loop in the early embryo.…”

Section: Introductionmentioning

confidence: 99%

Trophic signals acting via phosphatidylinositol-3 kinase are required for normal pre-implantation mouse embryo development

Chandrakanthan

Cahana

et al. 2004

Journal of Cell Science

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The growth and survival of the preimplantation mammalian embryo may be regulated by several autocrine trophic factors that have redundant or overlapping actions. One of the earliest trophic factors to be produced is embryo-derived platelet-activating factor (1-O-alky-2-acetyl-sn-glyceryl-3-phosphocholine). The addition of platelet-activating factor to embryo culture media exerted a trophic effect, but structurally related lipids (3-O-alky-2-acetyl-sn-glyceryl-1-phosphocholine, 1-O-alky-sn-glyceryl-3-phosphocholine, octadecyl-phosphocholine) had no effect. Platelet-activating factor induced a pertussis toxin-sensitive [Ca2+]i transient in two-cell embryos that did not occur in platelet-activating factor-receptor null (Pafr–/–) genotype embryos. Fewer Pafr–/– mouse zygotes developed to the blastocyst stage in vitro compared with Pafr+/+ zygotes (P<0.02), those that developed to blastocysts had fewer cells (P<0.001) and more cells with fragmented nuclei (P<0.001). The inhibition of 1-O-phosphatidylinositol 3-kinase (LY294002 (3 μM and 15 μM) and wortmannin (10 nM and 50 nM)) caused a dose-dependent inhibition of platelet-activating factor-induced [Ca2+]i transients (P<0.001). The two-cell embryo expressed 1-O-phosphatidylinositol 3-kinase catalytic subunits p110α, β, γ and δ, and regulatory subunits p85α and β. LY294002 and wortmannin each caused a significant reduction in the proportion of embryos developing to the morula and blastocyst stages in vitro, reduced the number of cells within each blastocyst, and significantly increased the proportion of cells in blastocysts with fragmented nuclei. The results indicate that embryo-derived platelet-activating factor (and other embryotrophic factors) act through its membrane receptor to enhance embryo survival through a 1-O-phosphatidylinositol 3-kinase-dependent survival pathway.

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“…Treatment of rodents during early pregnancy with a range of PAF-receptor antagonists reduced the incidence of successful implantation [9][10][11][12][13]. However, the failure of some investigators [14] to observe this effect, and the discovery by others [15] that the effective dose range of antagonists was very narrow, called into question the nature of the PAF receptor present in the early embryos.…”

Section: Introductionmentioning

confidence: 99%

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 Expression1

Stojanov

O’Neill

1999

Biology of Reproduction

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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.

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Antagonists of embryo-derived platelet-activating factor prevent implantation of mouse embryos

Abstract: Summary. Inhibitors

Cited by 75 publications

References 24 publications

Implantation potential and fetal viability of mouse embryos cultured in media supplemented with platelet-activating factor

Implantation potential and fetal viability of mouse embryos cultured in media supplemented with platelet-activating factor

Trophic signals acting via phosphatidylinositol-3 kinase are required for normal pre-implantation mouse embryo development

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 Expression1

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