A genomic and proteomic investigation of the impact of preimplantation factor on human decidual cells

Paidas, Michael J.; Krikun, Graciela; Huang, Su-Cheng; Jones, Richard C.; Romano, Michael F.; Annunziato, Jack; Barnea, Eytan R.

doi:10.1016/j.ajog.2010.03.024

Cited by 72 publications

(124 citation statements)

References 46 publications

(29 reference statements)

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“…The transcript XLOC_001837 was found to be upregulated in degenerate embryos (12-fold) compared with blastocysts (Table 2). This result is consistent with a previous report in which SORBS2 was found to be upregulated by the preimplantation factor in early stages of embryonic development (Paidas et al, 2010). The transcript XLOC_001206 located 3 kb downstream of the SOX9-like bovine gene showed a 38-fold difference in expression with more of this transcript present in degenerate embryos compared with blastocysts (Table 2).…”

Section: Resultssupporting

confidence: 92%

Novel transcripts and alternatively spliced genes are associated with early development in bovine embryos

Zhang

Peñagaricano

Chen

et al. 2012

Animal

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Infertility in cattle is a major concern of farmers worldwide and despite the enormous improvements in assisted reproduction technologies, the success rates of pregnancies are still low. Embryonic loss is considered one of the main factors of infertility in cattle. As such, the identification of genetic markers for embryo quality and development can help elucidate the molecular mechanisms involved in the formation of embryos with the highest developmental potential. In a previous study, using nextgeneration RNA sequencing, we identified novel transcripts and alternatively spliced genes that were associated with embryo quality. The objectives of this study were to characterize these transcripts and validate their expression in new biological replications of embryos using quantitative real-time PCR. Two types of embryos differing in morphological and developmental statuses (blastocysts and degenerate embryos) were produced using in vitro fertilization. Quantitative expression of eight novel transcripts revealed a range of 2.5-to 90-fold difference in expression between degenerate embryos and blastocysts. Some of these novel transcripts showed sequence similarity to human and cattle genes known to affect differentiation, growth and development. In addition, expression analysis of alternative splicing isoforms of five genes (MYL6, NOP10, RNF187, RPS24 and RPS28) revealed significant differential expression of these isoforms in the different embryo types. Thus, results of this study suggest that novel transcripts and alternatively spliced genes, found to be differentially expressed between blastocysts and degenerate embryos, can be used as markers for blastocyst formation and development.Keywords: embryo, fertility, gene expression, novel transcripts, alternative splicing ImplicationsOver the last 40 to 50 years there has been a significant decline in reproductive performance of dairy cattle, due in part to low fertilization rates and early embryonic loss. Although genetics plays an important role in embryo development, the identification of genes associated with embryo quality and pregnancy success has been a serious challenge. In this study, we characterized several genes that showed altered expression in preimplantation embryos that do not develop normally to the blastocyst stage. These genes can be used as candidate markers for embryo quality in cattle. IntroductionIn the last few decades, production of embryos by in vitro fertilization (IVF) has become a common practice for the treatment of infertility in both humans and cattle, and although IVF procedures are considered to be a true revolution in the field of fertility, the success rate of IVF pregnancies is still low. For example, in humans, , 8 out of 10 transferred embryos fail to implant successfully (Bromer and Seli, 2008), most likely because of the inability to identify embryos with the best development potential. In cattle, there has been a significant decline in fertility over the past few decades (Dobson et al., 2007;Leroy et al., 2008) because of low...

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Section: Resultssupporting

confidence: 92%

Novel transcripts and alternatively spliced genes are associated with early development in bovine embryos

Zhang

Peñagaricano

Chen

et al. 2012

Animal

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“…[5][6][7] PIF has been implicated in promoting embryo implantation through modulating maternal immune tolerance. 5,8,9 Consistent with the immune function, a synthetic PIF analog (sPIF) of 15 amino acids (MVRIKPG-SANKPSDD) that was subcutaneously administrated was able to both reverse and prevent paralysis through inhibiting neuroinflammation in a murine model of experimental autoimmune encephalomyelitis. 10 The neuroprotective property of sPIF was further underscored by its ability to mitigate neuronal loss and microglial activation in a rat model of perinatal brain injury.…”

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confidence: 95%

“…Given that sPIF induces global alterations in gene expression, it is highly likely that sPIF facilitates neuronal survival beyond targeting microRNA let-7. 9,11 To evaluate the neuroprotective potential of sPIF, we induced brain injury in neonatal rats at P2 (Figure 1a). This time point matches ongoing neuronal development.…”

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confidence: 99%

PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling

et al. 2015

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A synthetic peptide (sPIF) analogous to the mammalian embryo-derived PreImplantation Factor (PIF) enables neuroprotection in rodent models of experimental autoimmune encephalomyelitis and perinatal brain injury. The protective effects have been attributed, in part, to sPIF's ability to inhibit the biogenesis of microRNA let-7, which is released from injured cells during central nervous system (CNS) damage and induces neuronal death. Here, we uncover another novel mechanism of sPIF-mediated neuroprotection. Using a clinically relevant rat newborn brain injury model, we demonstrate that sPIF, when subcutaneously administrated, is able to reduce cell death, reverse neuronal loss and restore proper cortical architecture. We show, both in vivo and in vitro, that sPIF activates cyclic AMP dependent protein kinase (PKA) and calcium-dependent protein kinase (PKC) signaling, leading to increased phosphorylation of major neuroprotective substrates GAP-43, BAD and CREB. Phosphorylated CREB in turn facilitates expression of Gap43, Bdnf and Bcl2 known to have important roles in regulating neuronal growth, survival and remodeling. As is the case in sPIF-mediated let-7 repression, we provide evidence that sPIF-mediated PKA/PKC activation is dependent on TLR4 expression. Thus, we propose that sPIF imparts neuroprotection via multiple mechanisms at multiple levels downstream of TLR4. Given the recent FDA fast-track approval of sPIF for clinical trials, its potential clinical application for treating other CNS diseases can be envisioned.

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“…The presence of PIF in the maternal circulation has been correlated with live births in murine and bovine models (2)(3)(4). Despite the longstanding understanding that PIF is involved in promoting maternal immune tolerance and embryo implantation (2,(5)(6)(7)(8), the mechanism by which PIF does so has remained poorly understood. Recently, a synthetic PIF analog (sPIF) of 15 amino acids (MVRIKPGSANKPSDD) was reported to elicit neuroprotective effects in a murine model of experimental autoimmune encephalomyelitis (9).…”

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confidence: 99%

PreImplantation factor promotes neuroprotection by targeting microRNA let-7

Mueller

Zhou

Yang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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104

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Dysfunction and loss of neurons are the major characteristics of CNS disorders that include stroke, multiple sclerosis, and Alzheimer's disease. Activation of the Toll-like receptor 7 by extra-cellular micro-RNA let-7, a highly expressed microRNA in the CNS, induces neuronal cell death. Let-7 released from injured neurons and immune cells acts on neighboring cells, exacerbating CNS damage.Here we show that a synthetic peptide analogous to the mammalian PreImplantation factor (PIF) secreted by developing embryos and which is present in the maternal circulation during pregnancy inhibits the biogenesis of let-7 in both neuronal and immune cells of the mouse. The synthetic peptide, sPIF, destabilizes KH-type splicing regulatory protein (KSRP), a key microRNA-processing protein, in a Toll-like receptor 4 (TLR4)-dependent manner, leading to decreased production of let-7. Furthermore, s.c. administration of sPIF into neonatal rats following hypoxic-ischemic brain injury robustly rescued cortical volume and number of neurons and decreased the detrimental glial response, as is consistent with diminished levels of KSRP and let-7 in sPIF-treated brains. Our results reveal a previously unexpected mechanism of action of PIF and underscore the potential clinical utility of sPIF in treating hypoxic-ischemic brain damage. The newly identified PIF/TLR4/KSRP/ let-7 regulatory axis also may operate during embryo implantation and development.

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A genomic and proteomic investigation of the impact of preimplantation factor on human decidual cells

Cited by 72 publications

References 46 publications

Novel transcripts and alternatively spliced genes are associated with early development in bovine embryos

Novel transcripts and alternatively spliced genes are associated with early development in bovine embryos

PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling

PreImplantation factor promotes neuroprotection by targeting microRNA let-7

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