Abstract Body
Background/Aim: Endocrine disrupting chemicals (EDCs) such as phthalates have been reported to alter circulating lipid concentrations in animals, however, the relationship has rarely been investigated among humans. We assessed associations between phthalate metabolite biomarkers and lipidomic profiles among pregnant women (n = 99) in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) birth cohort.
Methods: We measured 19 urinary phthalate or phthalate replacement chemical metabolites during 24-28 weeks of pregnancy. Prenatal plasma lipidomic profiles were identified by liquid chromatography-mass spectrometry-based shotgun lipidomics. Multiple statistical strategies were used to assess relationships between phthalates and lipid profiles, including compound-by-compound comparisons using multiple linear regression and various dimension reduction techniques. We derived sums for each lipid class, sums for each lipid sub-class (saturated, monounsaturated, polyunsaturated), and used principal component analysis (PCA) to derive the principal component of each lipid class, which were then regressed on phthalates. Hierarchical clustering and multivariate analyses were also used for further investigation. False discovery rate (FDR) adjusted p-values (q-values) were used to account for multiple comparisons.
Results: A total of 587 unique lipids from 19 lipid classes were profiled. When controlling for multiple comparisons, 47 phthalate-lipid associations remained highly significant (p-value<0.001, q-value<0.1). Lipid patterns constructed from PCA accounted for 30~57% of the variation for each lipid class. Mono(2-ethyl-5-carboxypentyl) phthalate (MECCP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and the sum of dibutyl phthalates (ΣDBP) were associated with increased lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), and phosphatidic acid (PA) lipid groups, particularly those containing saturated and monounsaturated fatty acid chains. This is consistent with the top associations selected from the compound-by-compound analysis. Cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH) was also associated with higher polyunsaturated triglyceride (TG).
Conclusion: Certain phthalate/phthalate replacement biomarkers were associated with lipids integral to cell structure and function. Linking these lipid patterns with health parameters will be an important future step.
