Ascending Vaginal Infection in Mice Induces Preterm Birth and Neonatal Morbidity

Abstract

Preterm birth (PTB; delivery before 37 weeks), the main cause of neonatal death worldwide, can lead to adverse neurodevelopmental outcomes, as well as lung and gut pathology. PTB can be associated with ascending vaginal infection. Ascending Escherichia coli infection in pregnant mice induces PTB and reduces pup survival. The current study demonstrated 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. The utility of this model was validated by assessing the efficacy of maternal cervical gene therapy with an adeno-associated viral vector containing human β defensin 3. This improved pup survival and reduced tumor necrosis factor alpha mRNA expression in perinatal pup brains exposed to E. coli. This model provides a unique opportunity to evaluate the therapeutic benefit of preterm labor interventions on perinatal pathology.