The first three months of pregnancy are a chemical construction site: cells called trophoblasts must transform into specialised placental tissue, and a molecule called acetyl-coA is the fuel that loosens DNA to switch on the genes needed for that transformation. This matters because when that transformation fails, the placenta forms poorly, leading to preeclampsia—a complication affecting 6–8% of women that can trigger premature birth, restrict fetal growth, and raise mortality risk for both mother and child. Researchers know that acetyl-coA, generated from nutrients, both powers energy production and modifies histone proteins to control gene access. But they do not yet understand exactly how trophoblasts generate acetyl-coA, how that process drives cell specialisation, or whether it breaks down in preeclampsia. This project will trace those metabolic steps in the lab, then test whether the same steps are impaired in preeclamptic placentas and why. The findings will not produce a treatment tomorrow. But they will reveal the fundamental biochemical wiring that links what a mother eats to how her placenta forms—a piece of knowledge that could, down the line, point to early biomarkers or dietary interventions for a disorder that currently has no cure.
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Major pregnancy disorders originate from poor placental development in the first-trimester of pregnancy. Preeclampsia is a pregnancy-specific complication affecting 6-8% of women and can lead to premature delivery, fetal growth restriction, and increased risk of mortality to mother and child. A poorly functioning placenta caused by impaired placental formation in early pregnancy is implicated in the development of preeclampsia. Placental formation depends on cells called trophoblasts transforming into specialised cell-types. This process is dependent on the coordinated changes in sets of genes. Activation of these genes requires access to DNA regions that is determined by histone proteins that package DNA. Chemical modifications in histones influence their ability to package DNA. Specifically, addition of the molecule acetyl-coA leads to DNA loosening from histones facilitating gene activation. Acetyl-coA is generated from nutrients and used for energy production and histone modifications. I will examine the processes by which acetyl-coA is generated in trophoblasts and how these processes affect cell transformation and placental formation via modification of histone proteins. Moreover, I will investigate if these processes are impaired in preeclampsia and the causes of the impairments. The findings from this study are important for understanding how placental nutrient handling influences placental formation and will help us understand how this process is perturbed in a pregnancy disorder leading to poor outcomes in the mother and the baby.
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