Tina M F Dumont1, Jean-Francois Mouillet1, Avaraham Bayer1, Christina L Gardner2, William B Klimstra2, Dana G Wolf3, Simcha Yagel4, Fabiola Balmir5, Anna Binstock5, Joseph S Sanfilippo1, Carolyn B Coyne6, Jacob C Larkin1, Yoel Sadovsky7. 1. Magee-Womens Research Institute, Pittsburgh, PA, United States; Department of OBGYN and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, United States. 2. Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, United States; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, United States. 3. Clinical Virology Unit, Hadassah Medical Center, Hebrew University, Jerusalem, Israel. 4. Department of OBGYN, Hadassah-Hebrew University Medical Centers, Jerusalem, Israel. 5. Department of OBGYN and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, United States. 6. Magee-Womens Research Institute, Pittsburgh, PA, United States; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, United States. 7. Magee-Womens Research Institute, Pittsburgh, PA, United States; Department of OBGYN and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, United States; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, United States. Electronic address: ysadovsky@mwri.magee.edu.
Abstract
INTRODUCTION: We have previously shown that miRNAs produced from the Chromosome 19 MiRNA Cluster (C19MC), which are expressed almost exclusively in primate trophoblasts and are released into the maternal circulation, reduce viral replication in non-placental cells and can modulate migratory behavior of extravillous trophoblast. We sought to define the expression pattern of C19MC miRNA in early pregnancy and in response to viral infection in vitro and in vivo. METHODS: We prospectively followed women undergoing in vitro fertilization (IVF) and determined their blood level of C19MC miRNA using RT-qPCR. To examine the effect of viral exposure on C19MC miRNAs expression, we used three systems: (1) a transgenic mouse overexpressing the C19MC cluster and exposed to Togaviridae during pregnancy, (2) cultured primary human trophoblasts exposed to Vesicular Stomatitis Virus in vitro, and (3) amniotic fluid from women exposed to cytomegalovirus during pregnancy. RESULTS: In 27 IVF pregnancies, C19MC miRNAs were detected as early as 2 weeks after implantation, and their levels increased thereafter. There was no change in C19MC miRNA expression levels in the mouse placenta in response to viral exposure. Similarly, Vesicular Stomatitis Virus infection of primary human trophoblast did not selectively increase C19MC miRNA expression. C19MC miRNA expression in the amniotic fluid was not affected by vertical transmission of cytomegalovirus. DISCUSSION: The expression of C19MC miRNAs in maternal circulation very early in pregnancy suggests a role in the establishment of the maternal-fetal interface. The levels of C19MC miRNA are not influenced by diverse types of viral infection.
INTRODUCTION: We have previously shown that miRNAs produced from the Chromosome 19 MiRNA Cluster (C19MC), which are expressed almost exclusively in primate trophoblasts and are released into the maternal circulation, reduce viral replication in non-placental cells and can modulate migratory behavior of extravillous trophoblast. We sought to define the expression pattern of C19MC miRNA in early pregnancy and in response to viral infection in vitro and in vivo. METHODS: We prospectively followed women undergoing in vitro fertilization (IVF) and determined their blood level of C19MC miRNA using RT-qPCR. To examine the effect of viral exposure on C19MC miRNAs expression, we used three systems: (1) a transgenicmouse overexpressing the C19MC cluster and exposed to Togaviridae during pregnancy, (2) cultured primary human trophoblasts exposed to Vesicular Stomatitis Virus in vitro, and (3) amniotic fluid from women exposed to cytomegalovirus during pregnancy. RESULTS: In 27 IVF pregnancies, C19MC miRNAs were detected as early as 2 weeks after implantation, and their levels increased thereafter. There was no change in C19MC miRNA expression levels in the mouse placenta in response to viral exposure. Similarly, Vesicular Stomatitis Virus infection of primary human trophoblast did not selectively increase C19MC miRNA expression. C19MC miRNA expression in the amniotic fluid was not affected by vertical transmission of cytomegalovirus. DISCUSSION: The expression of C19MC miRNAs in maternal circulation very early in pregnancy suggests a role in the establishment of the maternal-fetal interface. The levels of C19MC miRNA are not influenced by diverse types of viral infection.
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