Maternal-fetal amino acid transfer across placenta in a mouse model of prenatal alcohol exposure

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Project Summary/Abstract The purpose for this supplement is to request a funded, 4-month extension for my current F32 award, from August 1st, 2021 to December 31st, 2021. Due to the COVID-19 pandemic, I was unable to continue performing experiments described in Aim 2 of my F32 project because the project under my current F32 award was not designated by my institution as essential research. Furthermore, I am a single mother with a young child, and the pandemic led to the shutdown of my child’s school and many afterschool programs in the local community. Without access to childcare, I had to spend a large amount of time homeschooling my child, which created an additional childcare responsibility and tremendous hardships that significantly hindered my research progress. The requested extension will compensate for the research time loss due to the pandemic, from March 2020 to July 2020. During this 4-month extension, I will complete the immunohistochemical experiments which investigate the cellular distribution of the amino acid (AA) transporters in the alcohol-exposed placentas, as described in Aim 2; these experiments would wrap up a manuscript. I will also finish analyzing the transcriptomic dataset generated from these alcohol-exposed placentas, another experiment described in Aim 2, for a second manuscript that is near-completion. The requested funds will cover my stipends during this 4- month extension period, research supplies needed to complete the immunohistochemistry, and fees for publishing the manuscripts reporting these results. The overall project hypothesis remains unchanged, which states that prenatal alcohol exposure (PAE) causes intrauterine growth restriction, at least in part, by reducing placental AA supply to the fetus, and that this is a consequence of downregulated placental mTOR signaling, AA transport, and altered AA metabolism. The three specific aims also remain unchanged. Aim 1 performs a comprehensive metabolomics analysis to characterize how PAE decreases AA supply and metabolic fate along the maternal-placental-fetal axis. Aim 2 performs transcriptomics analysis, western blotting and immunohistochemistry in the placenta to test the hypothesis that downregulation of placental AA transporters and metabolic genes contributes to the altered AA levels in PAE. Aim 3 performs western blotting in the placenta to test the hypothesis that these changes in AA transport and metabolism are accompanied by inhibition of placental mTOR pathways, which is a major regulator of AA availability and fetal growth. These studies use cutting-edge techniques to create a global portrait of how PAE affects placental AA supply and offer novel mechanistic insight into how PAE contributes to intrauterine growth restriction. The request extension will allow me to finish the proposed F32 research studies, which lay groundwork for future research that examines postnatal neural and metabolic health, the modulatory effect of genetic risk factors, and the effectiveness of maternal AA supplementation to improve outcomes of PAE pregnancies.