Effects of perfluorooctanoic acid (PFOA) exposure to pregnant mice on reproduction.

Perfluorooctanoic acid (PFOA) has similar characteristics to perfluorooctane sulfonate (PFOS) in reproduction toxicity featured by neonatal death. We found that PFOS exposure to mice during pregnancy led to intracranial blood vessel dilatation of fetuses accompanied by severe lung collapse which caused neonatal mortality. Thus, we adopted the corresponding experimental design to PFOS in order to characterize the neonatal death by PFOA. Pregnant ICR mice were given 1, 5 and 10 mg/kg PFOA daily by gavage from gestational day (GD) 0 to 17 and 18 for prenatal and postnatal evaluations, respectively. Five to nine dams per group were sacrificed on GD 18 for prenatal evaluation; other 10 dams were left to give birth. No maternal death was observed. The liver weight increased dose-dependently, with hepatocellular hypertrophy, necrosis, increased mitosis and mild calcification at 10 mg/kg. PFOA at 10 mg/kg increased serum enzyme activities (GGT, ALT, AST and ALP) with hypoproteinemia and hypolipidemia. PFOA treatment reduced the fetal body weight at 5 and 10 mg/kg. Teratological evaluation showed delayed ossification of the sternum and phalanges and delayed eruption of incisors at 10 mg/kg, but did not show intracranial blood vessel dilatation. Postnatal evaluation revealed that PFOA reduced the neonatal survival rate at 5 and 10 mg/kg. At 5 mg/kg pups were born alive and active and 16% died within 4 days observation, while all died within 6 hr after birth at 10 mg/kg without showing intracranial blood vessel dilatation. The cause of neonatal death by PFOA may be different from PFOS.

Neonatal death of mice treated with perfluorooctane sulfonate.

Pregnant mice exposure to perfluorooctane sulfonate (PFOS) causes neonatal death. Ten pregnant ICR mice per group were given 1, 10 or 20 mg/kg PFOS daily by gavage from gestational day (GD) 0 to the end of the study. Five dams per group were sacrificed on GD 18 for prenatal evaluation, the others were left to give birth. Additional studies were conducted for histopathological examination of lungs and heads of fetuses and neonates at birth. PFOS treatment (20 mg/kg) reduced the maternal weight gain and feed intake but increased the water intake. The liver weight increased in a dose-dependent manner accompanied by hepatic hypertrophy at 20 mg/kg. PFOS reduced the fetal body weight in a dose-dependent manner and caused a bilateral enlargement in the neck region in all fetuses at 20 mg/kg and mild enlargement in some fetuses at 10 mg/kg, in addition to skeletal malformations. Almost all fetuses at 20 mg/kg were alive on GD18 and showed normal lung structure; but at parturition, all neonates were inactive and weak, showed severe lung atelectasis and severe dilatation of intracranial blood vessel, and died within a few hours. At 10 mg/kg, all neonates were born alive, 27% showed slight lung atelectasis, all of them had mild to severe dilatation of the intracranial blood vessel, and 45% of neonates died within 24 hr. The cause of neonatal death in mice exposed to PFOS may be attributed either to the intracranial blood vessel dilatation or to respiratory dysfunction. The former might be a cause of the latter.