Maternal viral infection causes global alterations in porcine fetal microglia

Adrienne M. Antonson, Marcus A. Lawson, Megan P. Caputo, Stephanie M. Matt, Brian J. Leyshon, Rodney W. Johnson

Research output: Contribution to journalArticlepeer-review


Maternal infections during pregnancy are associated with increased risk of neurodevelopmental disorders, although the precise mechanisms remain to be elucidated. Previously, we established a maternal immune activation (MIA) model using swine, which results in altered social behaviors of piglet offspring. These behavioral abnormalities occurred in the absence of microglia priming. Thus, we examined fetal microglial activity during prenatal development in response to maternal infection with live porcine reproductive and respiratory syndrome virus. Fetuses were obtained by cesarean sections performed 7 and 21 d postinoculation (dpi). MIA fetuses had reduced brain weights at 21 dpi compared to controls. Furthermore, MIA microglia increased expression of major histocompatibility complex class II that was coupled with reduced phagocytic and chemotactic activity compared to controls. High-throughput gene-expression analysis of microglial-enriched genes involved in neurodevelopment, the microglia sensome, and inflammation revealed differential regulation in primary microglia and in whole amygdala tissue. Microglia density was increased in the fetal amygdala at 7 dpi. Our data also reveal widespread sexual dimorphisms in microglial gene expression and demonstrate that the consequences of MIA are sex dependent. Overall, these results indicate that fetal microglia are significantly altered by maternal viral infection, presenting a potential mechanism through which MIA impacts prenatal brain development and function.

Original languageEnglish (US)
Pages (from-to)20190-20200
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number40
StatePublished - Oct 1 2019


  • Maternal immune activation
  • Microglia
  • Neurodevelopment
  • Pig
  • Prenatal inflammation

ASJC Scopus subject areas

  • General


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