The Study Of Effects And Mechanism Of Perinatal PFOS Exposure On Hepatic Glucose Metabolism Of Rats Offspring

Objective: By establish rats model to examine effects of maternal exposure to PFOS during gestation and lactation on glucose metabolism of rats offspring. Methods: Pregnant Wistar rats were treated with doses of 0(control), 0.6(low) or 2(high) mg/kg/day PFOS respectively through gavage from gestation day 0(GD0) to postnatal day 21(PND21). We observed and recorded the general variations of rats; applied high performance liquid chromatography-mass spectrometry to detect serum PFOS concentrations; analyzed the trend of offspring’s body weight variation and organ coefficient; tested the oral glucose tolerance(OGTT) of offspring on PND21; observed the offspring’ morphology of liver and pancreas on PND21; measured hepatic gene expression of offspring on PND21 by biochip technology; compared fasting blood glucose and fasting serum insulin level at 9 weeks and 15 weeks; measured the expression of leptin and resistin genes. Results: The Serum PFOS concentrations increased to(16.00 ± 1.27) μg · mL-1 in the low-dose group and(80.54 ± 6.55)μg · m L-1 in the high-dose group on PND21(P<0.05),respectively. Compared with the control group, the body weight was significantly lower in male and female offsprings(P<0.05). The consequence of organ coefficient suggested that exposure to PFOS led to hepatomegaly and thymus atrophy(P<0.05). HE and oil red staining confirmed that offspring’ liver occured serious fatty degeneration in high dose group, but there was no pathological change in pancreas. The gene chip results showed that 581 gene and 20 signaling pathway were affected. Gene expression of SCD1 of PPAR delta singal pathway and Elovl6 were up-regulated significantly. Furthermore, the DUSP1 of JNK/SAPK singal pathway was down-regulated significantly. Through detecting the fasting plasma glucose and insulin level, the results indicated that both of them had hyperglycemia and hyperinsulinemia, especially in male rats. Compared with the control group, gene expression of glucose metabolism-related adipokine resistin was up-regulated and leptin was down-regulated significantly. Conclusion: PFOS impair glucose metabolism of offsprings by a variety of signaling pathways, directly or indirectly.It can also impair lipid metabolism led to insulin resistance. Adipocytokines contribute to the occurrence of glucose metabolism disorder. Our results suggest that maternal rats exposure to PFOS during pregnant and lactational period may contribute to glucose metabolic disorder in adulthood of offsprings and increase the risk of obesity, diabetes and metabolic syndrome.