Maternal IL-17A administration fails to disrupt fetal cortical lamination in the absence of maternal microbes

Abstract Maternal inflammation during pregnancy can disrupt fetal neurodevelopment and contribute to the pathogenesis of neurodevelopmental disorders. Interleukin-17A (IL-17A) has emerged as a potential mediator linking maternal immune activation (MIA) to neurodevelopmental abnormalities in offspring. Production of this cytokine is in-part regulated by the maternal gastrointestinal microbiome. However, it remains unclear whether IL-17A alone is sufficient to induce offspring brain abnormalities independent of maternal microbial signals. This study tests the potential for IL-17A to mediate fetal brain cortical architecture through administration of recombinant (r)IL-17A to pregnant germ-free (GF) dams. Pregnant GF mice received daily intraperitoneal injections of rIL-17A for six days, covering the mid- to latter half of the gestational period. Placental tissue was processed for histopathological evaluation, and cortical lamination was examined in the fetal brain using gold-standard immunohistochemical approaches. Spatial Light Interference Microscopy (SLIM), a novel label-free imaging technique, was employed to further quantify cortical architecture. This is the first report of SLIM imaging performed in the mouse embryonic brain. Overall, administration of rIL-17A to pregnant GF dams during mid-to-late gestation resulted in normal placental morphology and fetal cortical lamination patterns, suggesting that IL-17A alone is insufficient for altering cortical neurodevelopment, at least at this gestational timepoint. These findings highlight the importance of accounting for the maternal microbiome when interpreting the impacts of prenatal inflammation on brain development in utero. Competing Interest Statement The authors have declared no competing interest.