Transcriptional pathways linked to fetal and maternal hepatic dysfunction caused by gestational exposure to perfluorooctanoic acid (PFOA) or hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX) in CD-1 mice

A putative adverse outcome network for neonatal mortality and lower birth weight in rodents: Applicability to per‐ and polyfluoroalkyl substances and relevance to human health

“…During the fasting stage immediately after birth, glucose is initially supplied by hepatic glycogenolysis, followed by gluconeogenesis. Blake, Miller, et al (2022) exposed pregnant CD‐1 mice to PFOA or HFPO‐DA and analyzed maternal and fetal hepatic transcriptomes. The fetal liver showed more gene changes than did the maternal liver, and both exhibited enriched pathways including bile acid metabolism, peroxisome, fatty acid metabolism, adipogenesis, and oxidative phosphorylation.…”

“…If PPARα is activated both by HFPO‐DA and nutrient restriction, there may be a cumulative effect on hepatic glycogen depletion and neonatal hypoglycemia. The transcriptomic pathway analysis of maternal and fetal liver in pregnant mice treated with PFOA or HFPO‐DA by Blake, Miller, et al (2022) predicted several upstream regulators related to hepatic gluconeogenesis, perhaps indicating premature induction of gluconeogenesis. In contrast, Conley et al (2022) and Conley, Lambright, Evans, Medlock‐Kakaley, et al (2021) found no transcriptional changes in these genes in fetuses after gestational treatment with hydro‐PS acid or PFOS, and no effect on blood glucose or birth weight, even at a maternal dosage causing over 50% neonatal mortality.…”

Legacy and Emerging Per- and Polyfluoroalkyl Substances Surveillance in Bufo gargarizans from Inlet Watersheds of Chaohu Lake, China: Tissue Distribution and Bioaccumulation Potential

“…Its toxic effects have not been as well studied as PFOA, but limited data suggest that its exposure could alter lipid metabolism and liver dysfunction, and changed neonatal and maternal physiological parameters in rodents. 35,36 6:2 FTS was a novel PFOS alternative used globally in aqueous film-forming foams, which exhibited bioaccumulation potential and slow elimination and caused moderate hepatotoxicity in mice. 37 In this study, the elevated concentrations of certain emerging and precursor PFAS detected in tissues of the Chinese toads may cause their physiological toxicity.…”

Domestic Dogs and Horses as Sentinels of Per- and Polyfluoroalkyl Substance Exposure and Associated Health Biomarkers in Gray’s Creek North Carolina

“…Consequently, the production and use of shorter-chain alternatives, such as the perfluoroalkyl ether acid (PFEA) hexafluoropropylene oxide dimer acid (HFPO-DA), colloquially known as a GenX chemical, has increased. ,, Recent monitoring efforts have detected PFEAs in thousands of private wells in the eastern half of the state, including many in the Gray’s Creek area of southern Cumberland County NC, with concentrations of HFPO-DA exceeding the EPA’s drinking water health advisory limit of 10 parts per trillion (ppt; Table S1; Figure S2). − In conjunction with toxicity assessments for GenX chemicals finding evidence of adverse health effects in the liver, kidneys, thyroid, and immune system, there is considerable concern surrounding the potential long-term health impacts resulting from chronic consumption of PFAS-contaminated water. − However, the impacts of long-term exposure to the complex mixtures of PFAS found in the Gray’s Creek area remain unknown.…”