IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise

Science. 2019 Jul 12;365(6449):176-180. doi: 10.1126/science.aaw7733.


Elevated levels of type I interferon (IFN) during pregnancy are associated with intrauterine growth retardation, preterm birth, and fetal demise through mechanisms that are not well understood. A critical step of placental development is the fusion of trophoblast cells into a multinucleated syncytiotrophoblast (ST) layer. Fusion is mediated by syncytins, proteins deriving from ancestral endogenous retroviral envelopes. Using cultures of human trophoblasts or mouse cells, we show that IFN-induced transmembrane proteins (IFITMs), a family of restriction factors blocking the entry step of many viruses, impair ST formation and inhibit syncytin-mediated fusion. Moreover, the IFN inducer polyinosinic:polycytidylic acid promotes fetal resorption and placental abnormalities in wild-type but not in Ifitm-deleted mice. Thus, excessive levels of IFITMs may mediate the pregnancy complications observed during congenital infections and other IFN-induced pathologies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation / immunology*
  • Apoptosis Regulatory Proteins / immunology*
  • Cell Fusion*
  • Female
  • Fetal Death / etiology*
  • Fetal Resorption / immunology
  • Gene Products, env / immunology
  • Humans
  • Interferon Type I / immunology*
  • Intracellular Signaling Peptides and Proteins / immunology*
  • Mice
  • Poly I-C / pharmacology
  • Pregnancy
  • Pregnancy Proteins / immunology
  • RNA-Binding Proteins / immunology*
  • Trophoblasts / drug effects
  • Trophoblasts / immunology*


  • Antigens, Differentiation
  • Apoptosis Regulatory Proteins
  • Gene Products, env
  • IFIT2 protein, human
  • IFIT3 protein, human
  • Interferon Type I
  • Intracellular Signaling Peptides and Proteins
  • Pregnancy Proteins
  • RNA-Binding Proteins
  • leu-13 antigen
  • syncytin
  • Poly I-C