The associations between prenatal plastic phthalate exposure and lipid acylcarnitine levels in humans and mice

Phthalates are ubiquitous environmental pollutants known for their endocrine-disrupting properties, particularly during critical periods such as pregnancy and early childhood. Phthalates alter lipid metabolism, but the role of prenatal exposure on the offspring lipidome is less understood. In particular, we focused on long chain acylcarnitines - intermediates of fatty acid oxidation that serve as potential biomarkers of mitochondrial function and energy metabolism. This study aimed (i) to investigate the association between prenatal phthalate exposure and the child’s blood acylcarnitine concentrations and, (ii) to evaluate the impact of prenatal administration of di-(2-ethylhexyl) phthalate (DEHP) on acylcarnitine levels in mouse offspring blood, brain and liver. We conducted analyses of both a prospective birth cohort study and an experimental study in mice. From the Barwon Infant Study cohort (1074 mother-child pairs), prenatal phthalate exposure was assessed at 36 weeks' gestation and its association with acylcarnitine levels was examined in cord blood, and child’s blood at 6 months, 12 months and 4 years. In mice, pregnant C57BL/6 J mouse dams were exposed to 20 μg/kg DEHP for 5 days mid-gestation, and offspring tissues were analyzed at 1 month of age postnatally for acylcarnitine profiles. Our findings demonstrate that prenatal phthalate levels (specifically butyl benzyl phthalate (BBzP) and diisobutyl phthalate (DiBP)) are inversely associated with total long chain acylcarnitine levels in human cord blood at birth. In contrast, BBzP was positively associated with the long chain acylcarnitines at 12 months of age. In mice, prenatal DEHP exposure for only 5 days led to decreased palmitoylcarnitine (AC16:0) levels in the brain and liver, but not in blood. Taken together, our findings highlight that prenatal phthalate exposure can alter acylcarnitine profiles, indicating disruptions in fatty acid metabolism that may have long-term effects on metabolic health.