Adverse maternal and fetal outcomes in mouse models of prenatal infections

<ns3:p>Background 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. Methods Here we conducted a comparative analysis of four mouse models of prenatal infection: <ns3:italic>Toxoplasma gondii</ns3:italic> (intraperitoneal), vaccinia virus (intranasal), murine cytomegalovirus (intravenous) and influenza A virus (intranasal). Results We found markedly different effects on maternal morbidity and mortality, with <ns3:italic>T. gondii</ns3:italic> 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 <ns3:italic>T.gondii</ns3:italic> 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 <ns3:italic>T. gondii</ns3:italic> 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. Conclusions These models provide a systematic platform for understanding pathogen-specific mechanisms of pregnancy complications and identifying therapeutic targets.</ns3:p>