Gao Zhou, Xue Min, Wang Zhibiao
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.
Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, 410013, China.
BMC Pregnancy Childbirth. 2025 Apr 7;25(1):402. doi: 10.1186/s12884-025-07475-6.
Placental accreta spectrum (PAS) is a collective term for a range of pregnancy complications caused by abnormal placental implantation, posing a threat to the lives of both the mother and the fetus. This study aimed to screen for placental marker metabolites of PAS and assess the effect of L-Arginine on trophoblast invasion.
Placental tissues were collected from a total of 15 pregnant women, including 10 women diagnosed with PAS and 5 women with normal pregnancies. Histological staining was used to characterize pathological changes in the placenta. The changes in endogenous placental metabolites by LC-MS/MS. Subsequently, the role of marker metabolite L-Arginine on HTR-8/Svneo invasion was explored, and protein transcription and expression levels of GPRC6A/PI3K/AKT/MMP2/MMP9 were determined by RT-qPCR and western blot.
The placentas of PAS patients were mostly infiltrative invasion, with active proliferation and inhibited apoptosis of trophoblast cells. By LC-MS/MS, we identified 13 significantly different metabolites between healthy and PAS pregnant women's placenta tissue. Among them, placental concentrations of L-Arginine were significantly higher in PAS pregnant women than in controls. In vitro, L-Arginine promoted the proliferation and migration of HTR8/SVneo cells and upregulated the transcription and expression of proteins related to the GPRC6A/PI3K/AKT pathway.
Our study demonstrates that L-Arginine may promote trophoblast invasion and migration in placental implantation by upregulating the GPRC6A/PI3K/AKT pathway. This provides a new basis for screening appropriate metabolic markers for PAS, thus contributing to the prevention and treatment of PAS.
胎盘植入谱系障碍（PAS）是由胎盘植入异常引起的一系列妊娠并发症的统称，对母婴生命构成威胁。本研究旨在筛选PAS的胎盘标志物代谢物，并评估L-精氨酸对滋养细胞侵袭的影响。
共收集15例孕妇的胎盘组织，其中10例诊断为PAS，5例为正常妊娠。采用组织学染色来表征胎盘的病理变化。通过液相色谱-串联质谱法（LC-MS/MS）检测胎盘内源性代谢物的变化。随后，探讨标志物代谢物L-精氨酸对HTR-8/Svneo细胞侵袭的作用，并通过实时定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法测定GPRC6A/PI3K/AKT/MMP2/MMP9的蛋白质转录和表达水平。
PAS患者的胎盘大多为浸润性侵袭，滋养细胞增殖活跃且凋亡受抑制。通过LC-MS/MS，我们鉴定出健康孕妇和PAS孕妇胎盘组织之间有13种显著不同的代谢物。其中，PAS孕妇胎盘中L-精氨酸的浓度显著高于对照组。在体外，L-精氨酸促进了HTR8/SVneo细胞的增殖和迁移，并上调了与GPRC6A/PI3K/AKT途径相关的蛋白质的转录和表达。
我们的研究表明，L-精氨酸可能通过上调GPRC6A/PI3K/AKT途径促进胎盘植入过程中滋养细胞的侵袭和迁移。这为筛选PAS合适的代谢标志物提供了新依据，从而有助于PAS的防治。
