Latent, sex-specific metabolic health effects in CD-1 mouse offspring exposed to PFOA or HFPO-DA (GenX) during gestation.
Latent, sex-specific metabolic health effects in CD-1 mouse offspring exposed to PFOA or HFPO-DA (GenX) during gestation.
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DOI：
10.1016/j.emcon.2021.10.004
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发表时间：
2021
影响因子：
6
通讯作者：
Fenton SE
中科院分区：
文献类型：
--
作者：
Cope HA;Blake BE;Love C;McCord J;Elmore SA;Harvey JB;Chappell VA;Fenton SE
全氟辛酸（PFOA）是一种环境污染物，与发育中暴露的人群和小鼠模型的不良代谢结果有关。六氟环氧丙烷二聚酸（HFPO-DA，通常称为GenX）已在美国和欧洲的许多工业应用中取代了PFOA，并在全球水系统中测量了<1至9，350纳克/升的HFPO-DA。确定妊娠期暴露于GenX对雄性和雌性CD-1小鼠后代体重增加轨迹、成年代谢健康、肝脏病理学和关键脂肪基因途径的影响。向妊娠小鼠（妊娠第1.5-17.5天）每日口服GenX（0.2、1.0、2.0 mg/kg）、PFOA（0.1、1.0 mg/kg）或溶剂对照。后代在断奶时喂食高脂肪或低脂饮食（HFD或LFD），直至6周或18周尸检，并随时间推移测量代谢终点。评价PFOA和GenX血清和尿液浓度、体重增加、血脂参数、体重组成、葡萄糖耐量、白色脂肪组织基因表达和肝脏组织病理学。产前暴露于GenX导致其在5日龄幼仔的血清和尿液中蓄积（P = 0.007，P < 0.001），断奶时无法检测到。到18周龄时，与喂食LFD的对照雄性相比，喂食2.0 mg/kg GenX组LFD的雄性小鼠的体重增加（P < 0.05）、脂肪量（P = 0.016）、肝细胞微泡脂肪变化（P = 0.015）和胰岛素敏感性（P = 0.014）增加喂食LFD的对照雄性。与对照HFD雌性相比，喂食HFD的雌性小鼠在1.0 mg/kg GenX组（P = 0.022）和1.0 mg/kg PFOA组（P = 0.003）中肝细胞单细胞坏死显著增加。两种性别均受到妊娠期GenX暴露的影响;然而，观察到的表型在性别之间存在差异，男性表现出更多的代谢疾病特征，而女性则表现出对妊娠期暴露的肝损伤。产前暴露于1 mg/kg GenX和1 mg/kg PFOA会导致成年小鼠出现不良代谢结果，这些结果与饮食和性别有关。GenX还在幼鼠血清中积累，表明胎盘和潜在的哺乳转移是GenX的重要暴露途径。
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. 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. 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. 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. Prenatal exposure to 1 mg/kg GenX and 1 mg/kg PFOA induces adverse metabolic outcomes in adult mice that are diet- and sex-dependent. GenX also accumulated in pup serum, suggesting that placental and potentially lactational transfer are important exposure routes for GenX.
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DOI：
10.1016/j.reprotox.2013.07.017
发表时间：
2013-12
期刊：
Reproductive toxicology (Elmsford, N.Y.)
影响因子：
--
作者：
Angle BM;Do RP;Ponzi D;Stahlhut RW;Drury BE;Nagel SC;Welshons WV;Besch-Williford CL;Palanza P;Parmigiani S;vom Saal FS;Taylor JA
通讯作者：
Taylor JA
影响因子：
8.8
作者：
Darbre PD
通讯作者：
Darbre PD
影响因子：
10.4
作者：
Conley, Justin M.;Lambright, Christy S.;Gray, L. Earl, Jr.
通讯作者：
Gray, L. Earl, Jr.
影响因子：
29
作者：
Biddinger, Sudha B.;Hernandez-Ono, Antonio;Kahn, C. Ronald
通讯作者：
Kahn, C. Ronald
影响因子：
4.2
作者：
Bruce, Kimberley D.;Hanson, Mark A.
通讯作者：
Hanson, Mark A.