The key facts

  • Immune activation at day 12.5 of mouse pregnancy led to developmental abnormalities in about 30% of embryos within one day
  • All affected embryos turned out to be male; females and the remaining males developed without abnormalities
  • An inflammatory program was activated in the placentas of the affected males, with interleukin-6 identified as a necessary participant

What the researchers showed

A team from Cold Spring Harbor Laboratory described a mechanism by which immune activation during pregnancy rapidly disrupts placental function and the development of some male mouse embryos. The work, devoted to a model of neurodevelopmental disorders, was published in the journal Science Advances, as reported by Gazeta.Ru.

How the experiment was conducted

To study how a maternal inflammatory response affects the fetus, pregnant mice were injected with poly(I:C), a substance that mimics the immune response to a viral infection. The stage of 12.5 days of pregnancy proved especially sensitive: within just one day, about 30% of embryos showed developmental abnormalities — from reduced body mass to malformations of the sensory organs. All such cases occurred in some of the males, whereas the females and the remaining males in this model developed without such abnormalities.

What happened in the placenta

Analysis of cell nuclei revealed activation of inflammatory programs in the placentas of the affected males, with the most pronounced changes in spongiotrophoblasts — fetal-derived cells at the maternal-fetal interface. Under normal conditions, these cells help maintain immune tolerance of pregnancy. After exposure, the vulnerable males showed reduced activity of programs related to the extracellular matrix and hormone synthesis; this was accompanied by disruption of placental structure and an accumulation of immune cells and signaling molecules in the amniotic fluid. The inflammatory cytokine interleukin-6 turned out to be a necessary participant in the development of these abnormalities.

Context and limitations

The authors suggest that the described processes may help explain differences in susceptibility to inflammation during prenatal development. Earlier, as the outlet notes citing an October publication, scientists investigated why autism is diagnosed more often in males. However, the conclusions were obtained in a mouse model: the publication does not report confirmation of an analogous mechanism in humans.