The central role of creatine and polyamines in fetal growth restriction
Placental insufficiency is often associated with fetal growth restriction (FGR), a condition associated with both short- and long-term complications for the newborn. In this study, we performed comprehensive transcriptomic and metabolomic analyses to delineate the metabolic profiles that distinguish newborns with FGR from those born with appropriate-for-gestational- age (AGA) status. By comparing our RNA-seq data with placental transcriptome data from the POP dataset, we identified common enrichment categories, notably hypoxia, as well as alterations in creatine and arginine metabolism. In infants with FGR, placental insufficiency tends to promote anaerobic metabolism, resulting in limited ATP production. To counteract this deficiency, arginine is used to synthesise phosphocreatine, an energy-rich compound that is crucial for ATP production. Increased biosynthesis of polyamines  addition, our observations show an upregulation of SAT1 acetyltransferase that contributes to decreased concentrations of spermidine and N1-acetylspermidine as well as increased N1,N8-diacetylspermidine concentrations in the placenta of FGR infants. Increased .In summary, our study improves the understanding of metabolic adaptations associated with placental dysfunction in FGR and provides valuable insights for future therapeutic interventions. Overall design: Total RNA was extracted from 9 AGA (appropriate weights for gestational age), 9 SGA10 (small for gestational age, below the 10th percentile)  and 5 SGA3 (small for gestational age, below the 3rd percentile) term placenta.