Perfluorooctane sulfonate induces apoptosis of hippocampal neurons in rat offspring associated with calcium overload

The purpose of this research is to investigate the effects of perfluorooctane sulfonate (PFOS) on neuronal apoptosis in the hippocampus of rat offspring, and to elucidate the underlying mechanisms associated with calcium homeostasis. A cross-fostering model was established, enabling the evaluation of prenatal and postnatal exposure. Internal exposure was measured via PFOS concentration analysis in serum and the hippocampus. Cell apoptosis of hippocampus neurons was identified together with the measurement of intracellular free calcium concentration ([Ca2+](i)). Continuous PFOS exposure in both the prenatal and postnatal period induced increasing apoptosis in hippocampus neurocytes. Meanwhile, [Ca2+](i) increased in a dose dependent manner in the continuous exposure groups and prenatal exposure groups. Furthermore, expression of apoptosis related genes can be used for the mechanistic analysis of the apoptotic effects induced by PFOS. Both apoptosis linked gene-2 (alg-2) and death-associated protein kinase (dapk2) genes were up-regulated, especially in the prenatal exposure groups on postnatal day (PND) 35. B-cell CLL/lymphoma (Bcl-2) was also significantly up-regulated both on PND7 and PND35. Overall results indicated that PFOS exposure caused increasing of apoptosis in the hippocampus, where [Ca2+](i) overload acted as a potential mechanism. Furthermore, prenatal exposure resulted in long-lasting effects on calcium homeostasis and the genes' expression regulated calcium signaling and apoptosis of rat offspring, highlighting the developmental neurotoxicity risk of fetal PFOS exposure.