Raghuraman, N. | bioRxiv Science

bioRxiv2025

The Sphingosine-1-phosphate pathway is differentially activated in human gestational tissues.

BACKGROUNDDysregulated myometrial contractility contributes to obstetric complications. Sphingosine-1-phosphate (S1P) is an important inflammatory regulator in the myometrium and decidua, yet its metabolic dynamics during pregnancy are poorly characterized. This study aimed to profile the expression of S1P metabolic enzymes and receptors, and quantify sphingolipid metabolism in human gestational tissues across pregnancy. METHODSMyometrium, decidua parietalis, and chorioamnion were collected from women undergoing cesarean sections at term ([≥]37 weeks gestation) without labor (TNL), at term with labor (TL), and preterm (<37 weeks gestation) without labor (PTNL). Messenger RNA (mRNA) expression of S1P metabolic enzymes and receptors was assessed using quantitative polymerase chain reaction, while sphingolipids were quantified using targeted liquid chromatography-tandem mass spectrometry. RESULTSS1P metabolic enzymes and receptors were differentially expressed across gestational tissues. At TNL, SPHK1 expression was significantly higher in the decidua parietalis than in the chorioamnion and myometrium. The myometrium exhibited the highest mRNA expression of S1P receptors (S1PR1-4) compared to the decidua and chorioamnion. At term, S1P was more abundant in the myometrium than in the decidua parietalis and chorioamnion. Both SPHK1 and S1P were significantly increased in TL compared to TNL myometrium. S1P levels were higher in the myometrium at TNL compared to PTNL, while no significant differences were observed in the decidua and chorioamnion. Overall, sphingolipid metabolism was highest in the decidua and myometrium and lowest in the chorioamnion at term. CONCLUSIONThese findings reveal tissue-specific regulation of S1P metabolism and signaling in human gestational tissues, suggesting a therapeutic role of S1P in modulating myometrial contractility.

developmental biology↗

bioRxiv2023

Functional parcellation of the neonatal brain

The cerebral cortex is organized into distinct but interconnected cortical areas, which can be defined by abrupt differences in patterns of resting state functional connectivity (FC) across the cortical surface. Such parcellations of the cortex have been derived in adults and older infants, but there is no widely used surface parcellation available for the neonatal brain. Here, we first demonstrate that adult- and older infant-derived parcels are a poor fit with neonatal data, emphasizing the need for neonatal-specific parcels. We next derive a set of 283 cortical surface parcels from a sample of n=261 neonates. These parcels have highly homogenous FC patterns and are validated using three external neonatal datasets. The Infomap algorithm is used to assign functional network identities to each parcel, and derived networks are consistent with prior work in neonates. The proposed parcellation may represent neonatal cortical areas and provides a powerful tool for neonatal neuroimaging studies. HIGHLIGHTSO_LINeonatal cortical surface parcels derived based on abrupt changes in functional connectivity (FC) were highly homogenous and were validated in external neonatal datasets. C_LIO_LIBorders between cortical parcels were smoother (less abrupt) in group-average neonatal data compared to adults, likely due to increased heterogeneity in boundary location across individual neonates. C_LIO_LIParcels derived from adults and older infants show poor fit with neonatal resting-state FC data, underscoring the need for a neonatal-specific parcellation. C_LI

neuroscience↗