Prenatal exposure to perfluorooctanoic acid induces nerve growth factor expression in cerebral cortex cells of mouse offspring.

Previous studies have showed perfluorooctanoic acid (PFOA) inducing cytotoxicity in an organ. In addition, epidemiological data show that high level of PFOA in cord blood of a pregnant woman is detected. Therefore, we extrapolate that circulating PFOA may affect organogenesis in offspring, such as the brain. In this study, intrauterine exposure to PFOA in mice was used to characterize the potential impacts of prenatal PFOA exposure on cerebral cortex cells of postnatal 21 (PND21) offspring. In an ex vivo cell model, PND21-based cortex cells were exposed to PFOA or/and nerve growth factor (NGF)-specific inhibitor before further biochemical assays. As results, biochemical data showed increased trends of liver metabolic enzymes in sera of PFOA-treated PND21 mice. Interestingly, PFOA-treated PND21 mice resulted in increased levels of NGF in sera and cortex cells. In addition, PFOA-exposed cerebral cortex cells induced NGF and proliferating cell nuclear antigen (PCNA) expressions, while exposure to PFOA/NGF-specific inhibitor downregulated expressions of NGF and PCNA. In addition, Nissl-labeled, NGF-positive cells, and NGF protein expression in cortex cells of PFOA-treated PND21 mice were upregulated, respectively. Further, immunoblotting assays showed that intracephalic poly (ADP-ribose) polymerase (PARP) and p42/44 mitogen-activated protein kinase (MAPK) proliferation-regulated protein levels were elevated in PFOA-treated cortex cells. Taken together, our current findings indicate that the prenatal PFOA exposure may induce proliferation of cerebral cortex cells in PND21 mice through promoting intracephalic NGF expression in the cortex.