Vanegas Pineda, Sophia2026-01-232026-01-232026-01-23http://hdl.handle.net/10393/51307https://doi.org/10.20381/ruor-31701Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality, diagnosed after 20 weeks of gestation. Several subclasses of PE have been identified, each with distinct pathophysiology. Notably, the inflammation-mediated subclass (I-PE) is characterized by a pronounced increase in placental PARylation and a marked depletion of NAD+. This study investigates the mechanistic basis of this phenotype by profiling placental NAD+ -consuming enzymes and assessing whether selective inhibition of PARylating enzymes can restore trophoblast function and placenta health. HTR-8/SVneo trophoblast cells were exposed to TNF-α to mimic the I-PE inflammatory environment in vitro. Cells were also co-treated with Olaparib (a PARP1/2 inhibitor) or XAV939 (a PARP5a/5b inhibitor), as PARP1/2 and PARP5a/5b have been identified as key PARylating enzymes in the placenta. Total protein PARylation, cellular viability, mitochondrial func-on, and migratory capacity were assessed as cellular health and functional outcomes. TNF-α exposure increased total protein PARylation and impaired mitochondrial health by decreasing oxygen consumption rates during respiration, cellular viability and migration. Co- treatment with Olaparib reduced protein PARylation within 1h and restored cellular viability and migration, and mitochondrial respiration despite the continued pro-inflammatory conditions. In contrast, co-treatment with XAV939 showed no improvement in cellular health or function. These findings suggest that inflammation-induced PARP1/2 activation may contribute to placental PARylation and NAD+ depletion in I-PE and highlight the PARP1/2- NAD+ axis as a potential therapeutic target to improve placental health and func-on in affected pregnancies.enMetabolismPlacentaTrophoblastHTR-8PARPInflammationTNF-aSIRTSeahorse4HNEOXPHOSPreeclampsiaOxidative stressNADOlaparibThesis