Prenatal exposure to poly-/per-fluoroalkyl substances is associated with alteration of lipid profiles in cord-blood

Abstract

Introduction Poly-/per-fluoroalkyl substances (PFAS) are widespread environmental pollutants that may induce metabolic perturbations in humans, including particularly alterations in lipid profiles. Prenatal exposure to PFAS can cause lasting effects on offspring metabolic health, however, the underlying mechanisms are still unknown. Objectives The goal of the study was to investigate the impact of prenatal PFAS exposure on the lipid profiles in cord blood. Methods Herein, we combined determination of bile acids (BAs) and molecular lipids by liquid chromatography with ultra-high-resolution mass spectrometry, and separately quantified cord blood concentrations of sixteen PFAS in a cohort of Chinese infants (104 subjects) in a cross-sectional study. We then evaluated associations between PFAS concentration and lipidome using partial correlation network analysis, debiased sparse partial correlation, linear regression analysis and correlation analysis. Results PFAS levels showed significant associations with the lipid profiles; specifically, PFAS exposure was positively correlated with triacylgycerols (TG) and several bile acids. Importantly, exposure to perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) were associated with increased levels of TGs with saturated fatty acids while multiple classes of phospholipids were decreased. In addition, several free fatty acids showed significant positive correlations with PFOS. Conclusions Our results indicated that prenatal exposure to PFAS mediated metabolic changes, which may explain the associations reported between PFAS exposure and metabolic health later in life.

Changes in plasma levels of per- and polyfluoroalkyl substances (PFAS) are associated with changes in plasma lipids - A longitudinal study over 10 years

“…In another study, lipidomic analysis showed that PFAS levels were associated with increased bile acids and TGs with saturated fatty acids in cord blood. Worryingly, high levels of many of these lipids have been linked with several adverse health conditions, such as type 2 diabetes and non-alcoholic fatty liver disease, later in life (Sinisalu et al, 2021).Further, in a cohort of pregnant African American women, higher serum concentrations of PFNA was found to be associated with higher odds of small-for-gestational age (SGA) birth (OR = 1.32, 95% CI 1.07, 1.63), which can be a predictor of adult health risks such as metabolic syndrome and type 2 diabetes. Concomitantly, 10 overlapping metabolites, associated with both PFAS and fetal endpoints could be identified by a high resolution metabolomics workflow.…”

PFAS: forever chemicals—persistent, bioaccumulative and mobile. Reviewing the status and the need for their phase out and remediation of contaminated sites

“…Toxicokinetics Uptake via water, soil, plants, foodstuffs [99,183] Uptake Excretion via cord blood, breast milk and menstrual fluid [187] Excretion Higher PFAS concentrations in children than in adults [380][381][382][383][384] 1. Liver: hepatotoxic NAFLD, liver fibrosis, markers change [198,200,385,[386][387][388] 2. Kidney: nephrotoxic Reduced excretion of toxins [204,389,390]; increased incidence of CKD [203,391]; ferroptosis [392] 3.…”

“…Endocrinic system Thyroid [217,[394][395][396]; steroid(cortisone) [397][398][399] and sex hormones [398,400,401] 5. Metabolism (a) Glucose [402]; type 2-diabetes [403][404][405][406]; gestational diabetes [213] (b) Fat [387,[407][408][409] (c) Bile acid [387] (d) Total and non-HDL cholesterol [410][411][412] 6. Fertility: toxicity to reproduction, embryotoxic, fetotoxic (a) Delayed occurrence of desired pregnancy/childlessness [413,414] (b) Miscarriage [415] (c) Lifelong effects on organ health and development of disease [416][417][418][419][420][421][422] (c) Pregnancy/mother: hypertension [423], preeclampsia [423][424][425] (d) Pregnancy/child: miscarriage [139,426,427], reduced birth weight [195,196,428], reduced fetal growth …”

Perfluorooctanoic Acid-Disturbed Serum and Liver Lipidome in C57BL/6 Mice

“…Lipidomic studies have been performed in different living organisms to examine the health effect of PFOA, including C elegans, turtles, Atlantic cod, chicken eggs, and human cohort. , In a previous mouse study, PFOA at 3.5 mg/L in drinking water was provided to human peroxisome proliferator activated receptor α (hPPARα)-expressing mice fed an American diet . To the best of our knowledge, the lipidomic approach applied to the exposure study in the mouse model with a relatively low dose, especially at the ppb level, was not reported previously.…”