Placental Serum Amyloid A as a Therapeutic Target to Prevent Preterm Birth and Prematurity Related Morbidity

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Summary Preterm birth (PTB) and associated fetal brain injury bring about adverse perinatal outcomes including mortality in offspring, and high cost of care and treatment for the family and society. The pathologic immune responses in the placenta during maternal inflammation (MI) are thought to be the major causes of PTB and perinatal sequelae. Yet, the mechanisms are still not well understood because of the complexity of placental structure and function. Towards that end, there is a paucity of therapeutic agents capable of protecting offspring from exposure to MI. Serum amyloid A (SAA) has been identified as an inflammatory biomarker and its pathologic role has not been studied in the context of MI. Our published data demonstrated that one isoform, SAA2 was absent from the development in the placenta but highly susceptible to acute maternal inflammation. In this proposal, we plan to investigate the role of placental SAA isoforms in response to sub- chronic MI and explore whether inhibition of Saa2 systemically using small interfering RNA (siRNA) alleviates PTB and adverse offspring outcomes (Aim 1). Furthermore, we will compare the effect that whether administration of siRNA to Saa2 via targeted-placenta infusion will have higher efficacy and safety than via systemically infusion following sub-chronic maternal inflammation (Aim 2).The project will have a significant impact on the field of maternal-fetal medicine as it will provide placental SAA2 as a potential therapeutic target and will demonstrate a novel targeted-delivery route of siRNA to the placenta for the treatment of MI induced PTB and associated fetal brain injury.