The role of endogenous retroviruses in the formation of syncytiotrophoblast and materno-fetal barrier

Eva Ay, Ferenc Banati, Katalin Turi-Balog, Janos Minarovits

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Vertebrate genomes contain genetic elements, called endogenous retroviruses (ERVs), which are similar to the proviral genomes of extant exogenous retroviruses. The envelope proteins encoded by distinct human endogenous retrovirus (HERV) families are expressed in a cell-type- and developmental stage-specific manner in the placenta and their fusogenic activity contributes to the formation of the multinucleated syncytiotrophoblast layer from mononuclear cytotrophoblasts that surround the inner cell mass of the blastocyst. The syncytiotrophoblast layer constitutes the main materno-fetal barrier. It is indispensable for implantation and contributes, in a complex manner, to the protection of the fetus from the maternal immune response. Because of the rate of RNA transcription is unusually low in syncytiotrophoblast nuclei, the maintenance and growth of the syncytiotrophoblast layer depends on its continuous fusion with cytotrophoblasts. Syncytin-1, the envelope (Env) protein of the HERV-W family, is expressed specifically in the placental syncytiotrophoblast and initiates cell fusion by binding to its cognate receptors, the human sodium dependent neutral amino acid transporters ASCT2 and ASCT1 (neutral amino acid transporter type 2 and type 1 for Ala, Ser, Cys, Thr). Syncytin-2, the envelope protein encoded by the HERV-FRD family, uses the transmembrane protein MFSD2 (Major Facilitator Superfamily Domain Containing 2) to induce fusion of certain villous cytotrophoblasts. Syncytin-A and syncytin-B, two highly fusogenic Env proteins encoded by endogenous retrovirus sequences identified in the mouse genome also play a role in syncytiotrophoblast formation. Thus, it appears that as a result of convergent evolution, the protein products of independently acquired syncytin genes fulfill a similar physiological function in primate and rodent lineages. In addition, endogenous retrovirus Env proteins of rabbit and sheep are also instrumental in placental development. Inappropriate expression of HERVs, however, may have pathological consequences and appears to be associated with the development of certain autoimmune diseases, neoplasms and psychiatric syndromes.

Original languageEnglish
Title of host publicationMaternal Fetal Transmission of Human Viruses and their Influence on Tumorigenesis
PublisherSpringer Netherlands
Pages83-104
Number of pages22
Volume9789400742161
ISBN (Electronic)9789400742161
ISBN (Print)9400742150, 9789400742154
DOIs
Publication statusPublished - Oct 1 2012

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ay, E., Banati, F., Turi-Balog, K., & Minarovits, J. (2012). The role of endogenous retroviruses in the formation of syncytiotrophoblast and materno-fetal barrier. In Maternal Fetal Transmission of Human Viruses and their Influence on Tumorigenesis (Vol. 9789400742161, pp. 83-104). Springer Netherlands. https://doi.org/10.1007/978-94-007-4216-1_3