How Does Maternal Immune Activity Affect Fetal Survival and Brain Development?: The critical roles of IL-17A and microglia
DOI:
https://doi.org/10.51094/jxiv.861Keywords:
Autism Spectrum Disorder, Interleukin-17A, Maternal Immune Activation, Microglia, MiscarriageAbstract
Maternal immune activation (MIA) during pregnancy has been associated with increased risk of fetal loss and neurodevelopmental disorders in offspring. This review summarizes recent findings on the effects of MIA on fetal survival and microglial phenotype. Studies using polyinosinic-polycytidylic acid (poly(I:C))-induced MIA mouse models have revealed a crucial role for interleukin-17A (IL-17A) in mediating these effects. Overexpression of RORγt, a key transcription factor for IL-17A production, enhances poly(I:C)-induced fetal loss, possibly due to increased placental vulnerability. Intraventricular administration of IL-17A in fetal brains activates microglia and alters their localization, particularly in periventricular regions and the medial cortex. These activated microglia may contribute to abnormal synaptic pruning and excessive phagocytosis of neural progenitor cells, potentially leading to long-term neurodevelopmental abnormalities. The insights gained from MIA research have important clinical implications, including the potential for early identification of high-risk pregnancies and the development of novel preventive and therapeutic strategies. Future research should focus on elucidating the roles of other cytokines, determining critical periods of MIA susceptibility, and translating findings to human populations, while carefully considering ethical implications and the need for appropriate risk communication.
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Asumi Kubo
Sara Kamiya
Koki Higuchi
Kenyu Nakamura
Kyoko Kishi
Tetsuya Sasaki
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