Journal
TOXICOLOGY
Volume 462, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2021.152921
Keywords
Liver; Perfluoroalkyl substances (PFAS); Perinatal; Mixtures
Categories
Funding
- National Institute of Health [P42ES027706]
- National Science Foundation EPSCoR Cooperative Agreement [OIA-1655221]
- National Institute of General Medical Sciences of the National Institutes of Health [P20GM103430]
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PFAS chemicals, including PFOS, PFHxS, and PFOA, are widespread in the environment and have various effects on mouse dams and offspring liver and metabolism endpoints. Diet and PFAS exposure have distinct biological effects on mouse dams and offspring, with exposure to a high-fat diet leading to increased body weight in offspring.
Per- and polyfluoroalkyl substances (PFAS) are a family of chemicals that are ubiquitous in the environment. Some of these chemicals, such as perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonate (PFHxS) and perfluorooctanoic acid (PFOA), are found in human sera and have been shown to cause liver steatosis and reduce postnatal survival and growth in rodents. The purpose of this work is to evaluate the impact of diet and PFAS exposure to mouse dam (mus musculus) on the risk to pup liver and metabolism endpoints later in life, as well as evaluate PFAS partitioning to pups. Timed-pregnant dams were fed a standard chow diet or 60 % kcal high fat diet (HFD). Dams were administered either vehicle, 1 mg/kg PFOA, 1 mg/kg PFOS, 1 mg/kg PFHxS, or a PFAS mixture (1 mg/kg of each PFOA, PFOS, and PFHxS) daily via oral gavage from gestation day 1 until postnatal day (PND) 20. At PND 21, livers of dams and 2 pups of each sex were evaluated for lipid changes while remaining pups were weaned to the same diet as the dam for an additional 10 weeks. Dam and pup serum at PND 21 and PND 90 were also evaluated for PFAS concentration, alanine aminotransferase (ALT), leptin and adiponectin, and glycosylated hemoglobin A1c. Perinatal exposure to a HFD, as expected, increased pup body weight, maternal liver weight, pup liver triglycerides, pup serum ALT, and pup serum leptin. PFOA and the PFAS mixture increased liver weights, and. treatment with all three compounds increased liver triglycerides. The maternal HFD increased dam and pup serum PFAS levels, however, was protective against PFOA-induced increase in serum ALT and observed increases in liver triglycerides. The PFAS mixture had very distinct effects when compared to single compound treatment, suggesting some cumulative effects, particularly when evaluating PFAS transfer from dam to pup. This data highlights the importance of diet and mixtures when evaluating liver effect of PFAS and PFAS partitioning.
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