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bioRxiv · 10.1101/2025.05.27.656420

Influenza A virus infection during pregnancy increases transfer of maternal bloodborne molecules to fetal tissues

Gonzalez-Ricon, R. J.·Otero, A. M.·Chalen, I.·Savas, J.·Antonson, A. M.
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Abstract

Influenza A virus (IAV) infection during pregnancy is linked to heightened risk for neurodevelopmental disorders (NDDs) in the offspring. The precise pathophysiological mechanism(s) underling this association remains an active topic of research. We propose that maternal immune activation (MIA) triggered by IAV infection can disrupt selective permeability at the maternal-fetal interface, leading to increased transfer of blood-derived molecules into the fetal compartment. Some of these molecules might be responsible for the initiation of inflammatory cascades implicated in NDD etiology. Using a murine model of seasonal IAV infection during pregnancy, we examined placental and fetal brain barrier properties following maternal IAV challenge. Our findings demonstrate an enhanced transplacental transfer of fluorescently labeled tracers from maternal circulation to key neurodevelopmental regions, including the subventricular zone (SVZ) and choroid plexus (ChP) of fetal brains. This effect was most pronounced in fetuses from dams exposed to the highest dose of IAV. Notably, a similar pattern was observed for accumulation of the bloodborne neuroinflammatory molecule fibrinogen in these same brain regions, which was further amplified in response to the highest IAV dose. Moreover, fibrinogen accumulation was positively correlated with Iba1+ cell immunofluorescence, suggesting a potential interaction between fibrinogen and Iba1+ cells. Collectively, these findings suggest that IAV-induced MIA enhances transplacental transfer of blood-derived molecules into fetal tissues, potentially activating proinflammatory pathways in Iba1+ cells. HighlightsO_LIMaternal influenza infection increases fetal exposure to maternally derived tracers. C_LIO_LIFetal blood brain barrier dysfunction is evident in the SVZ and ChP. C_LIO_LIFibrinogen accumulation in the SVZ and ChP correlates with Iba1 intensity. C_LIO_LIIncreased vascular permeability may contribute to altered fetal brain development. C_LI

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Gonzalez-Ricon, R. J., Otero, A. M., Chalen, I., Savas, J., Antonson, A. M.. 2025-05-31. Influenza A virus infection during pregnancy increases transfer of maternal bloodborne molecules to fetal tissues. https://doi.org/10.1101/2025.05.27.656420

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