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Logo of retrovirBioMed CentralBiomed Central Web Sitesearchsubmit a manuscriptregisterthis articleRetrovirologyJournal Front Page
 
Retrovirology. 2011; 8(Suppl 2): O24.
Published online 2011 October 3. doi:  10.1186/1742-4690-8-S2-O24
PMCID: PMC3236869

Contribution of captured retroviral envelope genes, the "synctins" to the formation of the mouse placenta

Background

In most mammalian species, a key process of placentation is the fusion of trophoblast cells into a multinucleated syncytiotrophoblast layer at the fetomaternal interface. Envelope proteins of retroviral origin, the syncytins, specifically expressed in the placenta and with in vitro cell-cell fusogenic activity, have been suspected to be involved in this process [1-5]. In mice, inactivation of syncytin-A resulted in impaired formation of the syncytiotrophoblast layer I (facing the maternal blood lacuna) and in embryonic death [6], demonstrating that it is required for placenta development. Here, the effect of the inactivation of the second murine syncytin gene, syncytin-B, is described.

Materials and methods

We generated syncytin-B mutant mice, and embryos homozygous mutant for syncytin-B or for both syncytin-A and -B were obtained at different gestational stages, through time mating intercrosses. The placentae of syncytin-B null embryos were examined using histological analyses and refined electron microscopy analyses of the fetomaternal interface. Genes whose expression is modified in null placenta were identified using microarrays analyses and their expression was localized by immunohistochemistry.

Results

Syncytin-B null placenta disclose defects in formation of the syncytiotrophoblast layer II (facing the fetal blood vessels), with enlarged maternal lacuna disrupting the placenta architecture. At variance with the syncytin-A phenotype, syncytin-B null embryos are viable, although they still display late-onset embryonic growth retardation and a significant perinatal death rate. Interestingly, double SynA/SynB KO embryos die earlier than do embryos deficient for syncytin-A alone, suggesting cooperative interactions. Finally, an induction of connexin-30 expression was observed in the syncytin-B null placenta, with the protein being detected at the fetomaternal interface, suggesting a compensatory process whereby impaired syncytialization is counteracted by a gap junction mediated, cell-cell communication.

Conclusions

These findings demonstrate that syncytin-B is essential for syncytiotrophoblast formation and placenta integrity. Altogether, our data demonstrate that the two murine syncytins contribute independently to the formation of the two syncytial layers. Placenta formation is therefore a complex process that has taken advantage of independent and stochastic "captures" of retroviral sequences in the course of evolution to generate "appropriate" structures and functions. Some of them are absolutely required for pregnancy, whereas the other could still be amenable to compensatory processes.

References

  • Mi S. et al. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature. 2000;17:785–789. [PubMed]
  • Blond JL. et al. An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J Virol. 2000;74:3321–3329. doi: 10.1128/JVI.74.7.3321-3329.2000. [PMC free article] [PubMed] [Cross Ref]
  • Blaise S. et al. Functional characterization of two newly identified Human Endogenous Retrovirus coding envelope genes. Retrovirology. 2005;2:19. doi: 10.1186/1742-4690-2-19. [PMC free article] [PubMed] [Cross Ref]
  • Dupressoir A. et al. Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae. PNAS. 2005;102:725–730. doi: 10.1073/pnas.0406509102. [PubMed] [Cross Ref]
  • Heidmann O. et al. Identification of an endogenous retroviral envelope gene with fusogenic activity and placenta-specific expression in the rabbit: a new "syncytin" in a third order of mammals. Retrovirology. 2009;27:107. [PMC free article] [PubMed]
  • Dupressoir A. et al. Syncytin-A knockout mice demonstrate the critical role in placentation of a fusogenic, endogenous retrovirus-derived, envelope gene. PNAS. 2009;106:12127–12132. doi: 10.1073/pnas.0902925106. [PubMed] [Cross Ref]

Articles from Retrovirology are provided here courtesy of BioMed Central