The Developmental Toxicity Of Perfluorohexane Sulfonate During Pregnancy Via Disruption In Placental Lipid Homeostasis

Objective:Sodium perfluoro-1-hexanesulfonate(Sodiumperfluoro-1-hexanesulfonate,PFHx S)is one of the most abundant artificial compounds of perfluoroalkyl and polyfluoroalkyl substances.In existing studies,the developmental toxicity of this artificial compound during pregnancy is still poorly understood.This experiment aims to explore the developmental toxicity of PFHx S during pregnancy by disrupting placental lipid homeostasis.The study focuses on the highly influential and persistent developmental toxicity of early exposure to PFHx S during sensitive developmental stages in pregnancy,providing a foundation for further understanding of its impact on lipid metabolism and potential mechanisms.Method : The experimental research in this project mainly involves in vivo animal experiments.First,an animal model was established to verify the developmental toxicity of PFHx S exposure during the sensitive developmental stage in early pregnancy and the persistent effects of this chemical.In the animal experiment,the control group was given corn oil containing 0.03% DMSO by gavage according to the pregnant mouse’s weight,and the experimental group was given PFHx S by gavage according to the pregnant mouse’s weight.The low-dose group was administered 0.03mg/kg/day of0.03% DMSO corn oil,and the high-dose group was administered 0.3mg/kg/day of0.03% DMSO corn oil.The administration was given from gestational day 7(GD7)to gestational day 17,and no administration was given on the day of biological sampling.This project focused on the birth outcomes on the day of biological sampling,and randomly collected fresh and intact placental tissues from pregnant mice.The pathological images were observed and quantified by hematoxylin and eosin(H&E)staining.The LC-MS/MS technique was used to quantitatively measure the PFHx S content in maternal plasma,placenta,and fetal plasma.The placental lipidomics were determined using LC-MS/MS,and the transcriptome of the placenta was analyzed using transcriptomics.The placental homeostasis was analyzed by multi-omics integration analysis,and the expression of key lipid transporters(fabp2,fabp3,fatp1,and fatp2)in the placenta was finally detected.Result:In summary,exposure to low levels of PFHx S during pregnancy may increase the incidence of fetal death,in part by interfering with the placental lipid metabolism homeostasis.These findings highlight the importance of early sensitive developmental stages during pregnancy and raise concerns about persistent chemicals like PFHx S.They also provide a foundation for further understanding of the impact of PFHx S on pregnancy lipid metabolism and its potential mechanisms.