Lipidomic profiling of amniotic fluid reveals aberrant fetal lung development and fetal growth disrupted by lipid disorders during gestational asthma.

This study aimed to investigate how maternal asthma during pregnancy disrupts fetal lung development by altering lipid metabolism in the amniotic fluid, which is crucial for fetal development. A pregnancy-induced asthma model was established in female rats using house dust mite (HDM) as a common allergen. The fetuses were divided into four groups based on whether the mother and fetus were exposed to the allergen: PBS+PBS, PBS+HDM, HDM+PBS, and HDM+HDM. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to analyze changes in the lipid profile of the amniotic fluid and bronchoalveolar lavage fluid (BALF). Principal component analysis (PCA) and ChemRICH methods were used to explore the potential relationship between lipid metabolism abnormalities and impaired fetal lung development. The results indicate that maternal asthma exacerbates asthma-related inflammatory markers in fetuses, leading to pathological changes in the lungs and elevated levels of cytokines IL-5, IL-13, and IgE. Additionally, 18 differential lipids, primarily oxygenated lipids, were identified in the amniotic fluid after modeling, suggesting an enhanced oxidative stress environment for the fetus. This environment causes metabolic disturbances in various lipid groups in fetal lungs, with the HDM+HDM group showing significant abnormalities in lipids critical for lung development, including phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and fatty acids (FA). In conclusion, gestational asthma can reshape the lipid profile in the amniotic fluid and BALF, significantly disrupting fetal growth and lung development. Restoring normal lipid metabolism in the amniotic fluid and fetal lungs may offer a potential therapeutic approach to managing aberrant fetal lung development in asthmatic mothers.