Adverse maternal and fetal outcomes in mouse models of prenatal infections

Prenatal infections are a leading cause of adverse pregnancy outcomes, yet the mechanisms underlying pathogen-specific effects on maternal and fetal health remain poorly understood.

Here we conducted a comparative analysis of four mouse models of prenatal infection: Toxoplasma gondii (intraperitoneal), vaccinia virus (intranasal), murine cytomegalovirus (intravenous) and influenza A virus (intranasal).

We found markedly different effects on maternal morbidity and mortality, with T. gondii causing severe pregnancy-specific pathology leading to maternal mortality by 8 days post-infection, despite similar pathogen loads in pregnant and non-pregnant mice. Vaccinia virus caused prenatal morbidity, while cytomegalovirus and influenza induced only mild, transient effects. The maternal mortality in T.gondii infection was most likely due to immunopathology, while vaccinia virus caused prenatal morbidity possibly due to tissue infection. None of the pathogens directly infected the fetuses, yet both T. gondii and vaccinia virus significantly impaired both uterine vascular remodelling and fetal growth. Notably, pregnancy was found to be a modifier of local but not systemic immune responses, with reduced inflammatory cytokine production in uterine tissue of infected pregnant mice compared to non-pregnant controls.

These models provide a systematic platform for understanding pathogen-specific mechanisms of pregnancy complications and identifying therapeutic targets.