Phthalates have been reported to alter circulating lipid concentrations in animals, and investigation of these associations in humans will provide greater understanding of potential mechanisms for health outcomes.
To explore associations between phthalate metabolite biomarkers and lipidomic profiles among pregnant women (n = 99) in the Puerto Rico PROTECT cohort.
We measured 19 urinary phthalate metabolites during 24–28 weeks of pregnancy. Lipidomic profiles were identified from plasma samples by liquid chromatography-mass spectrometry-based shotgun lipidomics. Relationships between phthalate metabolites and lipid profiles were estimated using compound-by-compound comparisons in multiple linear regression and dimension reduction techniques. We derived sums for each lipid class and sub-class (saturated, mono-unsaturated, polyunsaturated) which were then regressed on phthalate metabolites. Associations were adjusted for false discovery.
After controlling for multiple comparisons, 33 phthalate-lipid associations were identified (False discovery rate adjusted p value < 0.05), and diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1 were the most strongly associated with multiple phthalate metabolites. Metabolites of di-2-ethylhexyl phthalate, bis(2-ethylhexyl) phthalate, dibutyl phthalates, and diisobutyl phthalate were associated with increased ceramides, lysophosphatidylcholines, lysophosphatidylethanolamines, and triacylglycerols, particularly those containing saturated and mono-unsaturated fatty acid chains.
Characterization of associations between lipidomic markers and phthalate metabolites during pregnancy will yield mechanistic insight for maternal and child health outcomes.
This study leverages emerging technology to evaluate lipidome-wide signatures of phthalate exposure during pregnancy.
The greatest lipid signatures of phthalate exposure were observed for diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1.
Polymerized glycerides are important for energy production and regulated through hormone signaling, while plasmenyl-phosphatidylcholines have been implicated in membrane dynamics and important for cell-to-cell signaling.
Characterization of these mechanisms are relevant for informing the etiology of maternal and children’s health outcomes.
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We thank the nurses and research staff who participated in cohort recruitment and follow up, as well as the Federally Qualified Health Centers (FQHC) and clinics in Puerto Rico who facilitated participant recruitment, including Morovis Community Health Center (FQHC), Prymed: Ciales Community Health Center (FQHC), Camuy Health Services, Inc. (FQHC), and the Delta OBGyn (Prenatal Clinic). This study was supported by the Superfund Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health (grants P42ES017198 and). Additional support was provided from NIEHS grant numbers P50ES026049, R01ES032203, and P30ES017885 and the Environmental influences on Child Health Outcomes (ECHO) program grant number UH3OD023251. Support for Max Aung was provided in part by NIH award P30ES030284.
The authors declare no competing interests.
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Ashrap, P., Aung, M.T., Watkins, D.J. et al. Maternal urinary phthalate metabolites are associated with lipidomic signatures among pregnant women in Puerto Rico. J Expo Sci Environ Epidemiol 32, 384–391 (2022). https://doi.org/10.1038/s41370-022-00410-3
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