Fetal membranes act as a barrier for adenoviruses: gene transfer into exocoelomic cavity of rat fetuses does not affect cells in the fetus

Laurema, Anniina; Vanamo, Kari; Heikkilä, Annaleena; Riekkinen, Mervi S.; Heinonen, Seppo; Ylä‐Herttuala, Seppo

doi:10.1016/j.ajog.2003.07.010

Cited by 6 publications

(5 citation statements)

References 19 publications

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“…The cardiovascular system showed in this study the most noticeable levels of expression throughout the whole pregnancy, but other organ systems were only found to express the transgene during late gestation (Schachtner et al 1999), which should be taken into account when designing protocols. Injection of an adenoviral vector into the placenta fail to induce detectable transgene expression in fetal organs (Senoo et al 2000), which, agreeing with the data by Laurema et al (2004), indicates that transgene expression is confined to the tissues in direct contact with the administered vector, making this an interesting approach for correcting placental defects, without affecting the fetus or the mother.…”

Section: Somatic Gene Therapy In Utero For Correcting Congenital Genesupporting

confidence: 76%

“…We found placenta transgene expression by injecting pregnant mice intra-peritoneally on day 5 of pregnancy (Zenclussen ML et al in revision). Accordingly, Laurema et al recently reported that the injection of LacZ-adenovirus into the exocoelomic cavity of rat fetuses led to expression of the gene expression on giant cells (the first trophoblast layer from rodents) while no transduction could be observed in fetuses or rat dams (Laurema et al 2004). These data confirm that the exocoelomic cavity does not offer a route for gene transfer into the fetus.…”

Section: The Route Of Administration Of the Vector Determines The Effmentioning

confidence: 88%

“…These data confirm that the exocoelomic cavity does not offer a route for gene transfer into the fetus. Fetal membranes may act as a barrier, which may naturally prevent adenoviral particles from passing between embryonic cavities (Laurema et al 2004). Although controversial, this would validate the use of gene therapy using adenoviral vectors in the exocoelomic cavity of rat fetuses during pregnancy aiming to express determined molecules at the fetal-maternal interface (placenta/decidua), avoiding the adenoviral passage to mother or fetus.…”

Section: The Route Of Administration Of the Vector Determines The Effmentioning

confidence: 99%

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The Use of Gene Therapy Tools in Reproductive Immunology Research

Zenclussen¹,

Zenclussen²,

Ritter³

et al. 2005

CGT

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Mammalian pregnancy is a complex phenomenon allowing the maternal immune system to support its allogeneic fetus, while still being effective against pathogens. Gene therapy approaches have the potential to treat devastating inherited diseases for which there is a little hope of finding a conventional cure. In reproductive medicine, experimental trials have been made so far only for correcting gene defects in utero. The use of gene therapy for improving pregnancy-rate success or avoiding pregnancy-related diseases i.e. miscarriage or pre-eclampsia, remains a very distant goal with unresolved moral and ethical aspects. However, gene therapy may help determining the role of several genes in supporting fetal growth and/or avoiding its rejection experimentally and might further help to identify new targets of intervention. Gene therapy strategies to avoid fetal rejection may include the transfer and expression of cyto-protective molecules locally at the fetal-placental interface. In addition, the ex-vivo genetic modification of immune cells for tolerance induction is a novel and tempting approach. In this regard, we have confirmed the role of the cyto-protective and immunomodulatory molecule Heme Oxygenase-1 (HO-1), by treating animals undergoing abortion with an adenovirus coding for HO-1. Since the sole application of a control vector did not provoke deleterious effects in pregnancy outcome, we propose the use of experimental gene therapy for unveiling molecular and cellular pathways leading to pregnancy success.

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Section: Somatic Gene Therapy In Utero For Correcting Congenital Genesupporting

confidence: 76%

Section: The Route Of Administration Of the Vector Determines The Effmentioning

confidence: 88%

Section: The Route Of Administration Of the Vector Determines The Effmentioning

confidence: 99%

See 1 more Smart Citation

The Use of Gene Therapy Tools in Reproductive Immunology Research

Zenclussen¹,

Zenclussen²,

Ritter³

et al. 2005

CGT

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“…Reichert's membrane is a specialized BM underlying the parietal endodermal cells. Linked to its suspected barrier role in the materno-fetal exchange, the absence of this structure could lead to lethality due to the toxic effect of direct exposure of the embryo to maternal blood circulation, uterine environment, or viral infection (Laurema et al, 2004;Williamson et al, 1997). It is worth noting that although Ln a1 in Reichert's membrane is produced by the parietal endodermal cells (Hogan et al, 1980;, the Ln-1 isoform must be important for two major processes: on the one hand for the differentiation of the parietal endodermal cells themselves as seen by the perturbation of their differentiation in the Ln a1 deleted embryos (visualized by the altered expression of cytokeratin), and on the other hand in inducing an overall cell survival signal to the embryos as seen by the high number of apoptotic cells in mutants, which could reflect an increase of anoikis in these cells.…”

Section: Discussionmentioning

confidence: 99%

Generation of a conditionally null allele of the laminin α1 gene

Alpy¹,

Jivkov²,

Sorokin³

et al. 2005

Genesis

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Laminins are heterotrimeric glycoproteins of the basement membranes. Laminin 1 (alpha1, beta1, gamma1) is the major laminin expressed during early mouse embryogenesis. To gain access to the physiological function of laminin alpha1 chain, we developed a conditionally null allele of its encoding gene (Lama1) using the cre/loxP system. Floxed-allele-carrying mice (Lama1(flox/flox)) display no overt phenotype. Lama1(flox/flox) mice were crossed with transgenic deleter mice (CMV-Cre) to generate Lama1-deficient mice (Lama1(Delta/Delta)). Lama1(Delta/Delta) embryos die during the early postimplantation period after embryonic day 6.5. They lack Reichert's membrane, an extraembryonic basement membrane in which laminin alpha1 is normally highly expressed. In parallel, Lama1(Delta/Delta) embryos display 1) parietal and visceral endoderm differentiation defects with altered expression of cytokeratin 19 and GATA4, respectively, and 2) an induction of apoptosis. This new mouse model is of particular interest as it will allow time- and tissue-specific inactivation of the Lama1 gene in various organs.

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“…When lacZ adenovirus was injected into the exocoelomic cavity between the amniotic and chorionic membranes, no transduction of fetal rat tissues was observed. 40 The skin of the human fetus begins to stratify at week 9 and completes keratinization by week 14. 41 The barrier function of the skin has been described as the 'raison d'être' of the epidermis.…”

Section: Innate Immune Mechanismsmentioning

confidence: 99%