Actions of platelet activating factor (PAF) on gametes and embryos: clinical aspects

1992 ◽  
Vol 4 (4) ◽  
pp. 399 ◽  
Author(s):  
IL Pike ◽  
AJ Ammit ◽  
C O'Neill
Keyword(s):  
Platelet Activating Factor ◽  
Preimplantation Embryos ◽  
Human Embryos ◽  
Clinical Aspects ◽  
Embryo Viability ◽  
Human Follicular Fluid ◽  
Body Tissues ◽  
Paf Antagonists ◽  
Human Ivf

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.

scholarly journals Immune factors in human embryo culture and their significance

Medicina ◽  
2010 ◽  
Vol 46 (4) ◽  
pp. 233 ◽  
Author(s):  
Živilė Čerkienė ◽  
Audronė Eidukaitė ◽  
Audronė Usonienė
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Platelet Activating Factor ◽  
Human Leukocyte ◽  
Preimplantation Embryos ◽  
Embryonic Cells ◽  
Embryo Viability ◽  
Transforming Growth Factor Α

There is increasing evidence that human development before implantation is regulated by embryonically and maternally derived growth factors. The “regulators” of embryonic origin such as soluble human leukocyte antigen G, platelet-activating factor, Th1/Th2 cytokines, insulinlike growth factor, epidermal growth factor, transforming growth factor α, colony-stimulating factor, platelet-derived growth factor may be used as indicators of embryo viability and implantation potential. The data prove the infl uence of growth factors on the development and growth of preimplantation embryos. Though there is a lot of research in the field of biomarkers during folliculogenesis and maternal-fetal interface, only few of them deal with regulators derived from embryonic cells to the cultivation medium. The aim of our study was to summarize the research dealing with immune markers produced by embryos in vitro and to estimate their impact on the cell growth, viability and implantation potential.

Metabolic and developmental responses of preimplantation embryos to platelet activating factor (PAF)

1992 ◽  
Vol 4 (4) ◽  
pp. 387 ◽  
Author(s):  
JP Ryan ◽  
C O'Neill ◽  
AJ Ammit ◽  
CG Roberts
Keyword(s):  
Culture Media ◽  
Platelet Activating Factor ◽  
Preimplantation Embryos ◽  
Human Embryos ◽  
Mouse Bioassay ◽  
Limiting Factor ◽  
Cell Stage ◽  
Culture In Vitro ◽  
Developmental Potential

Platelet activating factor (PAF) is an ether phospholipid produced by preimplantation embryos of a number of species. Production of PAF by embryos has been measured by detecting thrombocytopenia in a splenectomized mouse bioassay, platelet aggregation bioassays in vitro and a specific radioimmunoassay. Production is highly variable and is adversely affected by culture in vitro. It has, however, been correlated with morphology, development rates in vitro and the pregnancy potential of embryos following transfer. Investigations using PAF-antagonists have established an essential role for PAF in early pregnancy. Together with studies that have shown PAF to have direct effects on embryonic metabolism during culture in vitro, these observations suggest that PAF acts as an embryonic autocoid. Hence, a major site of action for embryo-derived PAF in vivo is the embryo itself. Supplementation of embryo culture media with PAF had no effect on the rate of development in vitro of 2-cell mouse embryos through to the blastocyst stage. However, PAF increased cell numbers of blastocysts cultured from the 2-cell stage and the mitotic index of embryos at both the 8-cell and blastocyst stages. Supplementation of culture media with PAF has also been shown to increase the implantation potential of both mouse and human embryos cultured in vitro. In the mouse, the effect of PAF in enhancing implantation rates was most evident when the developmental potential of untreated embryos was suboptimal. These observations suggest that the production of embryo-derived PAF is one limiting factor in maintaining the viability of embryos cultured in vitro.

Intracellular localisation of platelet-activating factor during mammalian embryo development in vitro: a comparison of cattle, mouse and human

2019 ◽  
Vol 31 (4) ◽  
pp. 658
Author(s):  
L. T. M. Vandenberghe ◽  
B. Heindryckx ◽  
K. Smits ◽  
M. Popovic ◽  
K. Szymanska ◽  
...  
Keyword(s):  
Platelet Activating Factor ◽  
Preimplantation Embryos ◽  
Mammalian Embryo ◽  
Developmental Potential ◽  
Nuclear Envelope Breakdown ◽  
Cytosolic Phospholipase ◽  
Carrier Molecule ◽  
Development In Vitro ◽  
Intracellular Localisation

Platelet-activating factor (PAF) is a well-known marker for embryo quality and viability. For the first time, we describe an intracellular localisation of PAF in oocytes and embryos of cattle, mice and humans. We showed that PAF is represented in the nucleus, a signal that was lost upon nuclear envelope breakdown. This process was confirmed by treating the embryos with nocodazole, a spindle-disrupting agent that, as such, arrests the embryo in mitosis, and by microinjecting a PAF-specific antibody in bovine MII oocytes. The latter resulted in the absence of nuclear PAF in the pronuclei of the zygote and reduced further developmental potential. Previous research indicates that PAF is released and taken up from the culture medium by preimplantation embryos invitro, in which bovine serum albumin (BSA) serves as a crucial carrier molecule. In the present study we demonstrated that nuclear PAF does not originate from an extracellular source because embryos cultured in polyvinylpyrrolidone or BSA showed similar levels of PAF in their nuclei. Instead, our experiments indicate that cytosolic phospholipase A2 (cPLA2) is likely to be involved in the intracellular production of PAF, because treatment with arachidonyl trifluoromethyl ketone (AACOCF3), a specific cPLA2 inhibitor, clearly lowered PAF levels in the nuclei of bovine embryos.

scholarly journals Regulation of Immunoglobulin G2 Production by Prostaglandin E2 and Platelet-Activating Factor

2000 ◽  
Vol 68 (3) ◽  
pp. 1563-1568 ◽  
Author(s):  
Yuichi Ishihara ◽  
Ji-Bo Zhang ◽  
Steve M. Quinn ◽  
Harvey A. Schenkein ◽  
Al M. Best ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Platelet Activating Factor ◽  
Pokeweed Mitogen ◽  
Cell Contact ◽  
Blood Leukocytes ◽  
Secreted Factors ◽  
Paf Antagonists ◽  
Localized Juvenile Periodontitis ◽  
Positive Regulators

ABSTRACT Patients with localized juvenile periodontitis (LJP) have elevated levels of immunoglobulin G2 (IgG2) in their sera. This is also observed in vitro when peripheral blood leukocytes from LJP patients are stimulated with pokeweed mitogen. In previous studies, we showed that lymphocytes from subjects with no periodontitis (NP subjects) produced substantial amounts of IgG2 when they were cultured with monocytes from LJP patients (LJP monocytes). These observations indicate that monocytes or monocyte-derived mediators are positive regulators of the production of IgG2. The present study was initiated to determine if secreted factors from LJP monocytes were capable of enhancing IgG2 production and to determine if prostaglandin E2 (PGE2), which LJP monocytes produce at elevated levels, enhances IgG2 production. Experiments in a transwell system and with monocyte-conditioned media indicated that cell-cell contact was not necessary for LJP monocytes to augment the production of IgG2 by T and B cells from NP subjects. Moreover, the production of IgG2 was selectively induced by the addition of PGE2 or platelet-activating factor (PAF), another lipid cytokine, which can elevate PGE2 synthesis. Furthermore, IgG2 production was abrogated when cells were treated with indomethacin, a cyclooxygenase inhibitor that blocks the synthesis of PGE2, or the PAF antagonists CV3988 and TEPC-15. The effects of indomethacin were completely reversed by PGE2, indicating that this is the only prostanoid that is essential for the production of IgG2. Similarly, PGE2 reversed the effects of a PAF antagonist, suggesting that the effects of PAF are mediated through the induction of PGE2 synthesis. Together, these data indicate that PGE2 and PAF are essential for the production of IgG2.

scholarly journals Transcription of paternal Y-linked genes in the human zygote as early as the pronucleate stage

Zygote ◽  
1994 ◽  
Vol 2 (4) ◽  
pp. 281-287 ◽  
Author(s):  
Asangla Ao ◽  
Robert P. Erickson ◽  
Robert M.L. Winston ◽  
Alan H Handysude
Keyword(s):  
Mammalian Species ◽  
Blastocyst Stage ◽  
Preimplantation Embryos ◽  
Human Embryos ◽  
Cell Stage ◽  
Gonad Differentiation ◽  
Embryonic Genome ◽  
Human Preimplantation Embryos

SummaryGlobal activation of the embryonic genome occurs at the 4– to 8–cell stage in human embryos and is marked by continuation of early cleavage divisions in the presence of transcriptional inhibitors. Here we demonstrate, using recerse transcripase–polymerase chin reaction (Rt–PCR), the presence of transcripts for wo paternal Y chromosomal genes, ZFY and SRY in human preimplantation embryos. ZFY transcripts were detected as early as the pronucleate stage, 20–24 h post-insemination In vitro and at intermediate stages up to the blastocyst stage. SRY Transcripts were also detected at 2–cell to blastocyos observed in many mammalian species focuses attention on the role of events in six determination prior to gonad differentiation.

STORAGE OF MAMMALIAN OOCYTES AND EMBRYOS: A REVIEW

1976 ◽  
Vol 56 (2) ◽  
pp. 131-145 ◽  
Author(s):  
RALPH R. MAURER
Keyword(s):  
Dimethyl Sulfoxide ◽  
Preimplantation Embryos ◽  
Embryo Viability ◽  
Cryoprotective Agent ◽  
Delayed Implantation ◽  
Rabbit Embryos

This article reviews the literature on storage of mammalian oocytes and embryos. Preimplantation embryos have been stored in vitro, in ligated oviducts and uteri of donor females, or in ligated oviducts of heterogenous females, and developed to term following transfer to suitable recipients. Embryo viability declined markedly after 48 h in storage anywhere other than in the reproductive tracts of species in which delayed implantation occurs naturally. Embryos stored at 0–37 C retained viability for 120 h; thereafter viability decreased. Storing oocytes in vitro at 10 C prolonged fertilizability for up to 3 days, but none developed to term if fertilized after 31 h storage. For successful storage, both cleavage and metabolism of embryos must be inhibited completely. This inhibition was accomplished with mouse and rabbit embryos by using dimethyl sulfoxide (DMSO) as the cryoprotective agent, slow rates of cooling (0.3–2 C/min) and warming (3–25 C/min), and a stepwise dilution of DMSO immediately after thawing. Neonates have resulted from the transfer of embryos previously frozen for 222 days.

scholarly journals Dynamics and clinical relevance of maternal mRNA clearance during the oocyte-to-embryo transition in humans

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Qian-Qian Sha ◽  
Wei Zheng ◽  
Yun-Wen Wu ◽  
Sen Li ◽  
Lei Guo ◽  
...  
Keyword(s):  
Mrna Decay ◽  
Meiotic Spindle ◽  
Preimplantation Embryos ◽  
Human Embryos ◽  
Developmental Potential ◽  
Maternal Mrna ◽  
Before And After ◽  
Maternal Transcripts ◽  
Human Preimplantation Embryos

Abstract Maternal mRNA clearance is an essential process that occurs during maternal-to-zygotic transition (MZT). However, the dynamics, functional importance, and pathological relevance of maternal mRNA decay in human preimplantation embryos have not yet been analyzed. Here we report the zygotic genome activation (ZGA)-dependent and -independent maternal mRNA clearance processes during human MZT and demonstrate that subgroups of human maternal transcripts are sequentially removed by maternal (M)- and zygotic (Z)-decay pathways before and after ZGA. Key factors regulating M-decay and Z-decay pathways in mouse have similar expression pattern during human MZT, suggesting that YAP1-TEAD4 transcription activators, TUT4/7-mediated mRNA 3ʹ-oligouridylation, and BTG4/CCR4-NOT-induced mRNA deadenylation may also be involved in the regulation of human maternal mRNA stability. Decreased expression of these factors and abnormal accumulation of maternal transcripts are observed in the development-arrested embryos of patients who seek assisted reproduction. Defects of M-decay and Z-decay are detected with high incidence in embryos that are arrested at the zygote and 8-cell stages, respectively. In addition, M-decay is not found to be affected by maternal TUBB8 mutations, although these mutations cause meiotic cell division defects and zygotic arrest, which indicates that mRNA decay is regulated independent of meiotic spindle assembly. Considering the correlations between maternal mRNA decay defects and early developmental arrest of in vitro fertilized human embryos, M-decay and Z-decay pathway activities may contribute to the developmental potential of human preimplantation embryos.

427. MDM2 maintains the latency of expression of TRP53 in the mouse preimplantation embryo

2008 ◽  
Vol 20 (9) ◽  
pp. 107
Author(s):  
X. Jin ◽  
V. Chandrakanthan ◽  
C. O.'Neill
Keyword(s):  
Preimplantation Embryo ◽  
Preimplantation Development ◽  
Signalling Pathway ◽  
Preimplantation Embryos ◽  
Normal Embryo ◽  
Embryo Viability ◽  
Preimplantation Embryo Development ◽  
Zygote Development ◽  
Dependent Inhibition

TRP53 is a tumour suppressor that causes cell-cycle arrest or cell death in response to a range of stressors. Normal preimplantation embryo development requires that TRP53 is maintained in a labile state1. Culture of mouse C57BL6 preimplantation embryos causes this latency to be breached and this is a cause of the low embryo viability following culture. MDM2 is an ubiquitin ligase that targets TRP53 for degradation by the proteosome. MDM2 is activated by Serine 166 phosphorylation (pMDM2). This is commonly catalysed by the phosphatidylinositol-3 kinase (PI3K) and AKT signalling pathway. A range of embryotrophins activate the PI3K and AKT pathway. This study tested the hypothesis that TRP53 is maintained in a latent state in the normal embryo by the activation of MDM2 by the actions of embryotrophins via a PI3K and AKT signalling pathway. Genetic deletion of Mdm2 prevents normal preimplantation development in a Trp53 dependent manner2. Addition of an MDM2 inhibitor (Nutlin-3) to culture medium caused a dose-dependent inhibition of zygote development (P < 0.001) that did not occur in Trp53−/−embryos. Immunofluorescence and western blot analysis detected pMDM2 throughout mouse preimplantation development. Zygote culture reduced the levels of pMDM2 formation. Furthermore, blocking the actions of Paf, PI3K or AKT in vitro reduced in the expression of pMDM2, and also resulted in higher levels of TRP53 expression in embryos. The embryopathy resulting from increased TRP53 could be partially ameliorated by the addition of the TRP53 antagonist α-pifithrin to media (P < 0.05). The results show MDM2 was activated by an embryotrophin (Paf), PI3K and AKT signalling pathway and was required for the latency of TRP53 expression in the preimplantation embryos. (1) Li A, Chandrakanthan V, Chami O, O’Neill C. (2007) Biology of Reproduction 76: 362–367. (2) Montes de Oca Luna R, Wagner DS, Lozano G. (1995) Nature 378: 203–205.

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