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

Area of Science:

• Reproductive Biology
• Biochemistry
• Obstetrics

Background:

• Dysregulated myometrial contractility is a key factor in obstetric complications.
• Sphingosine-1-phosphate (S1P) is a bioactive lipid influencing smooth muscle contractility, including uterine function.
• The metabolic dynamics of S1P during human pregnancy remain largely uncharacterized.

Purpose of the Study:

• To profile S1P metabolic enzymes and receptors in human gestational tissues throughout pregnancy.
• To quantify sphingolipid metabolites in the myometrium, decidua parietalis, and chorioamnion.
• To elucidate the role of S1P in regulating myometrial contractility.

Main Methods:

• Human gestational tissues (myometrium, decidua parietalis, chorioamnion) were collected from women undergoing cesarean sections at term without labor (TNL), term with labor (TL), and preterm without labor (PTNL).
• Messenger RNA (mRNA) expression of S1P metabolic enzymes and receptors was analyzed using quantitative polymerase chain reaction (qPCR).
• Sphingolipid metabolites were quantified using targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Main Results:

• S1P metabolic enzymes and receptors exhibited differential expression across gestational tissues.
• Sphingosine kinase 1 (SPHK1) expression was higher in the decidua parietalis compared to chorioamnion and myometrium in TNL pregnancies.
• The myometrium showed the highest mRNA expression of S1P receptors (S1PR1-4). S1P levels were higher in the myometrium during labor (TL) compared to non-labor (TNL) and preterm (PTNL) states.
• Overall sphingolipid metabolism was most active in the decidua and myometrium at term.

Conclusions:

• These findings highlight tissue-specific regulation of S1P metabolism and signaling within human gestational tissues.
• S1P plays a significant role in modulating myometrial contractility.
• S1P represents a potential therapeutic target for managing obstetric complications related to uterine contractility.