Observations of Apparent C-Type Particles in Baboon (
            <i>Papio cynocephalus</i>
            ) Placentas

Kalter, S. S.; Helmke, R; Panigel, M; Heberling, R. L.; Felsburg, Peter J.; Axelrod, Leonard R.

doi:10.1126/science.179.4080.1332

Cited by 112 publications

(36 citation statements)

References 8 publications

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“…In fact, the presence of viral particles in mammalian placentae has been documented in many species, including humans, baboons, and mice (25,26,29,39). Although it has been always assumed that these particles derive from ERVs expressed in the placenta, it is also possible, as shown in this study, that these particles are released from the uterine endometrium and then enter into the mononuclear trophectoderm cells of the gestating conceptus.…”

Section: Discussionmentioning

confidence: 78%

Viral Particles of Endogenous Betaretroviruses Are Released in the Sheep Uterus and Infect the Conceptus Trophectoderm in a Transspecies Embryo Transfer Model

Black

Arnaud

Burghardt

et al. 2010

J Virol

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The sheep genome contains multiple copies of endogenous betaretroviruses highly related to the exogenous and oncogenic jaagsiekte sheep retrovirus (JSRV). The endogenous JSRVs (enJSRVs) are abundantly expressed in the uterine luminal and glandular epithelia as well as in the conceptus trophectoderm and are essential for conceptus elongation and trophectoderm growth and development. Of note, enJSRVs are present in sheep and goats but not cattle. At least 5 of the 27 enJSRV loci cloned to date possess an intact genomic organization and are able to produce viral particles in vitro. In this study, we found that enJSRVs form viral particles that are released into the uterine lumen of sheep. In order to test the infectious potential of enJSRV particles in the uterus, we transferred bovine blastocysts into synchronized ovine recipients and allowed them to develop for 13 days. Analysis of microdissected trophectoderm of the bovine conceptuses revealed the presence of enJSRV RNA and, in some cases, DNA. Interestingly, we found that RNAs belonging to only the most recently integrated enJSRV loci were packaged into viral particles and transmitted to the trophectoderm. Collectively, these results support the hypothesis that intact enJSRV loci expressed in the uterine endometrial epithelia are shed into the uterine lumen and could potentially transduce the conceptus trophectoderm. The essential role played by enJSRVs in sheep reproductive biology could also be played by endometrium-derived viral particles that influence development and differentiation of the trophectoderm.

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Section: Discussionmentioning

confidence: 78%

Viral Particles of Endogenous Betaretroviruses Are Released in the Sheep Uterus and Infect the Conceptus Trophectoderm in a Transspecies Embryo Transfer Model

Black

Arnaud

Burghardt

et al. 2010

J Virol

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“…Electron microscopic studies reveal the presence of budding type C retrovirus-like particles in virtually every human normal term placenta examined (6)(7)(8)(9). This finding may have a parallel to the presence and location of endogenous retrovirus particles in the placentas of sub-human primate and other mammalian species (10)(11)(12). Nevertheless, in the absence of an established human placental retrovirus isolate, the biological nature of the retrovirus-like particles in human placentas remains unknown.…”

mentioning

confidence: 77%

Detection and immunochemical characterization of a primate type C retrovirus-related p30 protein in normal human placentas.

Jerabek¹,

Mellors²,

Elkon³

et al. 1984

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

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We find that 12 of 14 specimens of normal human term placentas analyzed by one-or two-dimensional electrophoresis and immunoblotting contain a protein or polypeptide of -30,000 daltons that is antigenically cross-reactive with p30 core protein of the simian sarcoma-associated virus/gibbon ape leukemia virus primate retrovirus group and is physicochemically similar to reference murine and primate type C retrovirus p30s. This finding may lead to an understanding of endogenous type C retrovirus gene expression in humans.Endogenous type C retroviruses are present in many mammalian species, including subhuman primates (1-4) among which the baboon (1, 5) has the closest evolutionary relation to man. These endogenous viruses exist as stable DNA proviruses that are integrated into the chromosomal DNA and are transmitted along with cellular genes in a Mendelian manner.

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“…To our surprise we found that all placenta samples, in contrast to brain, expressed PTN mRNA with 5Ј exons that are homologous to a human endogenous retrovirus (HERV) and are spliced onto the intact open reading frame (ORF) of PTN. Upon analysis of human genomic DNA, we located the insertion of an HERV fragment into the intron region upstream of the ORF of the human PTN gene expanding this region relative to the ancestral PTN gene shared with other nonprimate species.HERV-like particles were identified more than two decades ago in human oocytes, teratocarcinoma cells, and mammary carcinoma tissues, as well as in placenta, and retroviral transcripts were detected in a number of tissues and cell lines (13)(14)(15)(16)(17). These findings reflect the high number of HERV fragments found integrated throughout the human genome (several thousand copies).…”

mentioning

confidence: 99%

“…HERV-like particles were identified more than two decades ago in human oocytes, teratocarcinoma cells, and mammary carcinoma tissues, as well as in placenta, and retroviral transcripts were detected in a number of tissues and cell lines (13)(14)(15)(16)(17). These findings reflect the high number of HERV fragments found integrated throughout the human genome (several thousand copies).…”

mentioning

confidence: 99%

Human trophoblast and choriocarcinoma expression of the growth factor pleiotrophin attributable to germ-line insertion of an endogenous retrovirus

Schulte

Lai

Kurtz

et al. 1996

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

193

151

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Retroviral elements are found in abundance throughout the human genome but only rarely have alterations of endogenous genes by retroviral insertions been described. Herein we report that a human endogenous retrovirus (HERV) type C is inserted in the human growth factor gene pleiotrophin (PTN) between the 5 untranslated and the coding region. This insert in the human genome expands the region relative to the murine gene. Studies with promoterreporter constructs show that the HERV insert in the human PTN gene generates an additional promoter with trophoblastspecific activity. Due to this promoter function, fusion transcripts between HERV and the open reading frame of PTN (HERV-PTN) were detected in all normal human trophoblast cell cultures as early as 9 weeks after gestation (n ‫؍‬ 7) and in all term placenta tissues (n ‫؍‬ 5) but not in other normal adult tissues. Furthermore, only trophoblast-derived choriocarcinoma cell lines expressed HERV-PTN mRNA whereas tumor cell lines derived from the embryoblast (teratocarcinoma) or from other lineages failed to do so. We investigated the significance of HERV-PTN mRNA in a choriocarcinoma model by targeting this transcript with ribozymes and found that the depletion of HERV-PTN mRNA prevents human choriocarcinoma growth, invasion, and angiogenesis in mice. This suggests that the tissue-specific expression of PTN due to the HERV insertion in the human genome supports the highly aggressive growth of human choriocarcinoma and possibly of the human trophoblast.Pleiotrophin (PTN) is a secreted heparin-binding polypeptide growth factor (1) with mitogenic (1-3) and transforming effects (3) on fibroblasts and growth factor activity on epithelial (2, 4, 5) and endothelial (2, 5, 6) cells. Furthermore, PTN induces the release of proteolytic enzymes from endothelial cells (7) and stimulates neurite outgrowth (8) and tube formation by endothelial cells in vitro (5) as well as angiogenesis in the rabbit corneal pocket assay (6). PTN gene expression is regulated in a time-and tissue-specific manner during rodent development and PTN mRNA is found at high levels in the central nervous system during the perinatal period, is downregulated thereafter, and is present at low levels in a few adult tissues (1, 9-11). On the other hand, the PTN gene is upregulated in several human tumor tissues and tumor cell lines (2) but little is known about the regulatory elements in this gene (12).To understand the mechanisms that regulate expression of the human PTN gene, we studied 5Ј ends of PTN mRNA isolated from various human tissues that express the PTN gene. To our surprise we found that all placenta samples, in contrast to brain, expressed PTN mRNA with 5Ј exons that are homologous to a human endogenous retrovirus (HERV) and are spliced onto the intact open reading frame (ORF) of PTN. Upon analysis of human genomic DNA, we located the insertion of an HERV fragment into the intron region upstream of the ORF of the human PTN gene expanding this region relative to the ancestral PTN gene share...

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Observations of Apparent C-Type Particles in Baboon ( Papio cynocephalus ) Placentas

Abstract: Ultrastructural investigations have revealed the presence of apparent endogenously derived C-type particles in the placental villi of each of 13 baboons studied. Both budding and mature forms were observed in the syncytiotrophoblast of these animals at various stages of pregnancy.

Cited by 112 publications

References 8 publications

Viral Particles of Endogenous Betaretroviruses Are Released in the Sheep Uterus and Infect the Conceptus Trophectoderm in a Transspecies Embryo Transfer Model

Viral Particles of Endogenous Betaretroviruses Are Released in the Sheep Uterus and Infect the Conceptus Trophectoderm in a Transspecies Embryo Transfer Model

Detection and immunochemical characterization of a primate type C retrovirus-related p30 protein in normal human placentas.

Human trophoblast and choriocarcinoma expression of the growth factor pleiotrophin attributable to germ-line insertion of an endogenous retrovirus

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