Ascending vaginal infection in mice induces preterm birth and neonatal morbidity

Abstract

Preterm birth (PTB; delivery <37 weeks), the main cause of neonatal death worldwide, can lead to adverse neurodevelopmental outcomes, as well as lung and gut pathology. PTB is commonly associated with ascending vaginal infection. Previously, we have shown that ascending E. coli infection in pregnant mice induces PTB and reduces pup survival. Here, we demonstrate that this model recapitulates the pathology observed in human preterm neonates, namely neuroinflammation, lung injury and gut inflammation. In neonatal brains, there is widespread cell death, microglial activation, astrogliosis and reduced neuronal density. We also validate the utility of this model by assessing efficacy of maternal cervical gene therapy with an adeno-associated viral vector containing human beta defensin 3; this improves pup survival and reduces Tnf mRNA expression in perinatal pup brains exposed to E. coli. This model provides a unique opportunity to evaluate the therapeutic benefit of preterm labour interventions on perinatal pathology.