The adverse effects of perinatal exposure to nonylphenol on carbohydrate metabolism in male offspring rats

Abstract

Background: We sought to investigate the adverse effects of perinatal exposure to nonylphenol (NP) on carbohydrate metabolism of male offspring rats. Methods: Thirty-two healthy pregnant Sprague Dawley rats were randomly divided into four groups, control normal diet group (C), NP normal diet group (NPN), control high-energy diet group (CH), and NP high-energy diet group (NPH). Both of the control groups were received a gavage of corn oil and the NP-groups were received NP (200 mg/kg/day) from gestational days 6 to post-natal day (PND) 21. The concentrations of NP in pancreatic tissues were measured by high-performance liquid chromatography (HPLC). The key genes of glucose metabolism expression were detected by reverse transcription-polymerase chain reaction (RT-PCR). The pancreatic tissues were stained with hematoxylin/eosin (HE). Results: On PND 1, the body weights of male pups in the NPN and NPH groups were lower than those of the CH group (p = 0.012 and 0.001, respectively). On PND 30, the body weight of male pups from the NPH group was elevated compared with the C group (p = 0.019), while the body weights of male pups in the NPN and NPH groups were elevated compared to the CH group (p = 0.034 and 0.004, respectively). On PND 60, the body weights of NPN and NPH pups were higher than those in the C (p < 0.001) and CH groups (p < 0.001). The levels of fasting blood glucose (FBG) were increased significantly in the animals treated with NP compared to control animals (F = 29.14, p < 0.001). The FBG levels in the treatment groups are ranked as follows: NPH > NPN > CH > C (p < 0.05). The concentrations of NP in pancreas tissues in both the NPN (2045.0 ± 130.1 μg/L) and NPH groups (2038.0 ± 104.2 μg/L) were higher than those in the C (499.5 ± 27.4 μg/L) and CH groups (494.2 ± 22.4 μg/L; p < 0.05). Morphological examination of tissues from rats exposed to NP shown that the NP-treated groups appeared to have a higher degree of inflammatory injury, edema, and focal necrotic cells in the pancreatic tissues. Compared with C group, expression of glucokinase (GCK) was down-regulated, while Uncoupling protein-2 (UCP-2) was up-regulated in the NP-treated groups (F_GCK = 218.89, p < 0.001; F_UCP-2 = 18.82, p < 0.001). Conclusions: Prenatal exposure to NP could induce glucose metabolism disorder in male F1 rats, which may be due to the fact that NP induces abnormal expression patterns of GCK and UCP-2.

Keywords:

• Nonylphenol
• diabetes
• pancreas
• metabolic syndrome