Ascending Vaginal Infection in Mice Induces Preterm Birth and Neonatal Morbidity

Area of Science:

• Reproductive Biology
• Neonatal Pathology
• Microbiology

Background:

• Preterm birth (PTB) is the primary cause of neonatal mortality globally.
• PTB is linked to neurodevelopmental issues, lung and gut pathologies, and ascending vaginal infections.
• Ascending Escherichia coli infection in pregnant mice is a known inducer of PTB and reduced pup survival.

Purpose of the Study:

• To validate a mouse model for recapitulating human preterm birth pathology.
• To assess the therapeutic efficacy of maternal cervical gene therapy in this PTB model.

Main Methods:

• Induction of ascending E. coli infection in pregnant mice.
• Pathological analysis of neonatal brains, lungs, and guts.
• Maternal cervical gene therapy using an adeno-associated viral vector with human β defensin 3.

Main Results:

• The mouse model successfully replicated human preterm neonate pathologies, including neuroinflammation, lung injury, and gut inflammation.
• Neonatal brains exhibited cell death, microglial activation, astrogliosis, and reduced neuronal density.
• Gene therapy improved pup survival and decreased TNF-α mRNA in E. coli-exposed brains.

Conclusions:

• The E. coli-induced PTB mouse model effectively mimics human perinatal pathologies.
• Maternal gene therapy with human β defensin 3 shows therapeutic potential for PTB.
• This model is valuable for evaluating interventions for preterm labor and associated pathologies.