Vacy Kristina, Rupasinghe Thusi, Bjorksten Alicia, Gogos Andrea, Meikle Peter J, Burugupalli Satvika, Boon Wah Chin, Ponsonby Anne-Louise
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, Australia; Melbourne School of Population and Global Health, University of Melbourne, Parkville 3010, Australia.
SCIEX, Mulgrave 3170, Australia.
Reprod Toxicol. 2025 Mar;132:108835. doi: 10.1016/j.reprotox.2025.108835. Epub 2025 Jan 10.
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.
邻苯二甲酸盐是普遍存在的环境污染物，因其具有内分泌干扰特性而闻名，尤其是在孕期和幼儿期等关键时期。邻苯二甲酸盐会改变脂质代谢，但产前暴露对后代脂质组的作用尚不太清楚。我们特别关注长链酰基肉碱——脂肪酸氧化的中间产物，它可作为线粒体功能和能量代谢的潜在生物标志物。本研究旨在（i）调查产前邻苯二甲酸盐暴露与儿童血液中酰基肉碱浓度之间的关联，以及（ii）评估产前给予邻苯二甲酸二（2-乙基己基）酯（DEHP）对小鼠后代血液、大脑和肝脏中酰基肉碱水平的影响。我们对一项前瞻性出生队列研究和一项小鼠实验研究都进行了分析。从巴旺婴儿研究队列（1074对母婴）中，在妊娠36周时评估产前邻苯二甲酸盐暴露情况，并在脐带血以及儿童6个月、12个月和4岁时的血液中检查其与酰基肉碱水平的关联。在小鼠中，怀孕的C57BL/6 J母鼠在妊娠中期5天内每天暴露于20 μg/kg的DEHP，产后1个月时分析后代组织的酰基肉碱谱。我们的研究结果表明，产前邻苯二甲酸盐水平（特别是邻苯二甲酸丁苄酯（BBzP）和邻苯二甲酸二异丁酯（DiBP））与出生时人类脐带血中总长链酰基肉碱水平呈负相关。相比之下，BBzP与12个月大时的长链酰基肉碱呈正相关。在小鼠中，产前仅5天暴露于DEHP会导致大脑和肝脏中棕榈酰肉碱（AC16:0）水平降低，但血液中未出现这种情况。综上所述，我们的研究结果突出表明，产前邻苯二甲酸盐暴露可改变酰基肉碱谱，表明脂肪酸代谢受到干扰，这可能对代谢健康产生长期影响。
