Differential effects of different time windows of postnatal perfluorooctane sulfonate exposure on cognitive development in mouse hippocampus

Perinatal perfluorooctane sulfonate (PFOS) exposure of the next generation through placenta and breast milk has been highly concerned. Epidemiological and animal studies have reported that perinatal PFOS exposure is associated with neurodevelopmental disorders such as learning and autism spectrum disorders in children. However, the sensitive time window of perinatal PFOS exposure for neurodevelopment has yet to be elucidated. Here we examined differential effects of different time windows of postnatal PFOS exposure (postnatal day (PD) 1-7 or 8-14) on cognitive development and gene expression profiles in the hippocampus. Pups were exposed to PFOS from PD 1 to 7 (PD 1-7 group) or from PD 8-14 (PD 8-14 group) through breastfeeding by dams who received a daily gavage of 1 mg/kg body weight PFOS per day during each period. Object location test and object recognition test revealed the impairment in spatial memory in PD 1-7 group at PD 70. Learning ability was also retarded in visual discrimination test. According to RNA-seq analysis and real-time PCR, Serpina3g and Tmem91 were significantly downregulated in the hippocampus of PD 1-7 group at PD 21. These results suggest that the first 7 days after birth is critically vulnerable to PFOS exposure and consequent neurodevelopmental deficits rather than the late phase of postpartum. Our work puts a strong emphasis on the importance of monitoring PFOS concentration in pregnant women and potential impact on retardation of neurodevelopment in children. Overall design: To examine the sensitive time window of perinatal PFOS exposure for neurodevelopment, we generated 2 different mouse models with different PFOS exposure periods (PD 1-7 and 8-14). Pups were exposed to PFOS from PD 1 to 7 or from PD 8-14 through breastfeeding by dams who received a daily gavage of 1 mg/kg body weight PFOS per day during each period. Pups were then assessed by behavior test battery for evaluating higher brain functions. RNA-seq was performend using RNA samples extracted from mouse hippocampal tissues sampled at postnatal day 21 from each group to investigate the differential effects of lactaional PFOS exposure periods on gene expression profiles.