Yuqi Yang, Xia Li, Fang Guo, Jian Zhang, Jiuxiang Fan, Wei Zhu, Bin Yu
After adjustment for blood glucose levels, persistent lipid metabolic abnormalities were observed in mothers, fetuses, and at the maternal-fetal interface. These findings suggest a potential regulatory role of the placenta in the transmission of maternal lipid disturbances to the fetus, which may serve as a key organ associated with GDM-related fetal metabolic dysregulation.
BACKGROUND: This study aimed to characterize lipid profiles in maternal serum, placenta, and umbilical cord serum from patients with gestational diabetes mellitus (GDM), clarify lipid metabolic disturbances at the maternal-fetal interface, and identify key molecules associated with the intergenerational metabolic inheritance of GDM.
METHOD: Lipidomic profiling was performed using tandem mass spectrometry (MS/MS) in maternal serum, placental tissue, and umbilical cord serum. Orthogonal partial least squares discriminant analysis (OPLS-DA) was applied to compare lipid metabolic differences between GDM and control groups. Potential biomarkers were screened using combined multivariate and univariate analyses. Partial least squares structural equation modeling (PLS-SEM) was further used to evaluate lipid transmission and correlative associations across the maternal-fetal interface.
RESULT: In total, 331, 246, and 301 lipid species were identified in maternal serum, placental tissue, and umbilical cord blood, respectively. OPLS-DA revealed distinctly different lipid profiles between groups in all three compartments, with the most pronounced separation in maternal serum. Thirteen, eight, and five differential lipids serving as potential biomarkers were identified in the three sample types, respectively. KEGG analysis showed that these differential lipids were significantly enriched in glycerophospholipid metabolism. PLS‑SEM results indicated that most maternal lipids showed no significant correlation with fetal lipid levels, and only phosphatidylinositol (PI) exhibited a significant positive correlation between maternal serum and umbilical cord blood. Lysophosphatidylethanolamine (LPE) exerted a significant positive correlation in the placental‑to‑fetal pathway. In addition, phosphatidylcholine (PC, C18), sphingomyelin (SM), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) exhibited significant positive correlations in the maternal‑to‑placental pathway.
CONCLUSION: After adjustment for blood glucose levels, persistent lipid metabolic abnormalities were observed in mothers, fetuses, and at the maternal-fetal interface. These findings suggest a potential regulatory role of the placenta in the transmission of maternal lipid disturbances to the fetus, which may serve as a key organ associated with GDM-related fetal metabolic dysregulation.