Mbadhi Magdaleena Naemi, Fujiwara Hideji, Gill Ruth, Mitchum Kaci T, Lin Cici, Raghuraman Nandini, Frolova Antonina I
Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
bioRxiv. 2025 Jun 5:2025.06.02.657487. doi: 10.1101/2025.06.02.657487.
Dysregulated 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.
Myometrium, 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.
S1P metabolic enzymes and receptors were differentially expressed across gestational tissues. At TNL, expression was significantly higher in the decidua parietalis than in the chorioamnion and myometrium. The myometrium exhibited the highest mRNA expression of S1P receptors () compared to the decidua and chorioamnion. At term, S1P was more abundant in the myometrium than in the decidua parietalis and chorioamnion. Both 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 ands chorioamnion. Overall, sphingolipid metabolism was highest in the decidua and myometrium and lowest in the chorioamnion at term.
These findings reveal tissue-specific regulation of S1P metabolism and signaling in human gestational tissues, suggesting a therapeutic role of S1P in modulating myometrial contractility.
子宫肌层收缩功能失调会导致产科并发症。鞘氨醇-1-磷酸(S1P)是子宫肌层和蜕膜中一种重要的炎症调节因子,但其在孕期的代谢动态特征尚不明确。本研究旨在剖析S1P代谢酶和受体的表达情况,并对整个孕期人类妊娠组织中的鞘脂代谢进行定量分析。
收集足月(≥37周妊娠)未临产(TNL)、足月临产(TL)及早产(<37周妊娠)未临产(PTNL)行剖宫产的女性的子宫肌层、壁蜕膜和绒毛膜羊膜。采用定量聚合酶链反应评估S1P代谢酶和受体的信使核糖核酸(mRNA)表达,同时采用靶向液相色谱-串联质谱法定量鞘脂。
S1P代谢酶和受体在不同妊娠组织中的表达存在差异。在TNL时,壁蜕膜中的表达显著高于绒毛膜羊膜和子宫肌层。与蜕膜和绒毛膜羊膜相比,子宫肌层中S1P受体的mRNA表达最高。足月时,子宫肌层中的S1P比壁蜕膜和绒毛膜羊膜中的更丰富。与TNL子宫肌层相比,TL时的 和S1P均显著增加。与PTNL相比,TNL时子宫肌层中的S1P水平更高,而在蜕膜和绒毛膜羊膜中未观察到显著差异。总体而言,足月时鞘脂代谢在蜕膜和子宫肌层中最高,在绒毛膜羊膜中最低。
这些发现揭示了人类妊娠组织中S1P代谢和信号传导的组织特异性调节,提示S1P在调节子宫肌层收缩方面具有治疗作用。