Latent, sex-specific metabolic health effects in CD-1 mouse offspring exposed to PFOA or HFPO-DA (GenX) during gestation  

作　　者：Harlie A.Cope Bevin E.Blake Charlotte Love James McCord Susan A.Elmore Janice B.Harvey Vesna A.Chappell Suzanne E.Fenton 

机构地区：[1]National Toxicology Program Laboratory,Division of the National Toxicology Program(DNTP),National Institutes of Environmental Health Sciences(NIEHS),National Institutes of Health(NIH),Research Triangle Park,NC,USA [2]Multimedia Methods Branch,Center for Environmental Measurement and Modeling,Office of Research and Development,U.S.Environmental Protection Agency,RTP,NC,USA [3]Cellular and Molecular Pathology Branch,DNTP,NIEHS,NIH,RTP,NC,USA

出　　处：《Emerging Contaminants》2021年第1期219-235,共17页新兴污染物（英文）

基　　金：funded by NIEHS/DNTP(Z01-ES102785[S.E.F.]).

摘　　要：Background:Perfluorooctanoic acid(PFOA)is an environmental contaminant associated with adverse metabolic outcomes in developmentally exposed human populations and mouse models.Hexafluoropropylene oxide-dimer acid(HFPO-DA,commonly called GenX)has replaced PFOA in many industrial applications in the U.S.and Europe and has been measured in global water systems from<1 to 9350 ng/L HFPO-DA.Health effects data for GenX are lacking.Objective:Determine the effects of gestational exposure to GenX on offspring weight gain trajectory,adult metabolic health,liver pathology and key adipose gene pathways in male and female CD-1 mice.Methods:Daily oral doses of GenX(0.2,1.0,2.0 mg/kg),PFOA(0.1,1.0 mg/kg),or vehicle control were administered to pregnant mice(gestation days 1.5-17.5).Offspring were fed a high-or low-fat diet(HFD or LFD)at weaning until necropsy at 6 or 18 weeks,and metabolic endpoints were measured over time.PFOA and GenX serum and urine concentrations,weight gain,serum lipid parameters,body mass composition,glucose tolerance,white adipose tissue gene expression,and liver histopathology were evaluated.Results:Prenatal exposure to GenX led to its accumulation in the serum and urine of 5-day old pups(P=0.007,P<0.001),which was undetectable by weaning.By 18 weeks of age,male mice fed LFD in the 2.0 mg/kg GenX group displayed increased weight gain(P<0.05),fat mass(P=0.016),hepatocellular microvesicular fatty change(P=0.015),and insulin sensitivity(P=0.014)in comparison to control males fed LFD.Female mice fed HFD had a significant increase in hepatocyte single cell necrosis in 1.0 mg/kg GenX group(P=0.022)and 1.0 mg/kg PFOA group(P=0.003)compared to control HFD females.Both sexes were affected by gestational GenX exposure;however,the observed phenotype varied between sex with males displaying more characteristics of metabolic disease and females exhibiting liver damage in response to the gestational exposure.Conclusions:Prenatal exposure to 1 mg/kg GenX and 1 mg/kg PFOA induces adverse metabolic outcomes in adult mic

关 键 词：PFOA HFPO-DA GenX Gestational exposure Metabolism PFAS Microvesicular fatty change 

分 类 号：X503[环境科学与工程—环境工程]