Effects of perinatal exposure to nonylphenol on delivery outcomes ofpregnant rats and inflammatory hepatic injury in newborn rats

摘要

The current study aimed to investigate the effects of perinatal exposure to nonylphenol (NP) on delivery outcome of pregnant rats and subsequent inflammatory hepatic injury in newborn rats. The pregnant rats were divided into 2 groups: control group (corn oil) and NP exposure group. Thirty-four pregnant rats were administered NP or corn oil by gavage from the sixth day of pregnancy to 21 days postpartum, with blood samples collected at 12 and 21 days of pregnancy and 60 days after delivery. The NP concentration was measured by HPLC, with chemiluminescence used for detection of estrogen and progesterone levels. Maternal delivery parameters were also observed. Liver and blood of the newborn rats were collected and subjected to automatic biochemical detection of liver function and blood lipid analyzer (immunoturbidimetry), and ultrastructural observation of the hepatic microstructure, with the TNF-α and IL-1β hepatic tissue levels evaluated by immunohistochemistry. Compared with the control group, the pregnant and postpartum serum NP and estradiol levels of the mother rats in the NP group were significantly increased, together with lowered progesterone level, increased number of threatened abortion and dystocia, and fewer newborn rats and lower litter weight. Serum and hepatic NP levels of the newborn rats measured 60 days after birth were significantly higher than those of thecontrol group, as well as lower testosterone levels and increased estradiol levels.When observed under electron microscope, the hepatocyte nuclei of the control groupwere large and round, with evenly distributed chromatin. The chromatin of hepatocytesin the NP group presented deep staining of the nuclei, significant lipid decrease inthe cytoplasm, and the majority of cells bonded with lysate. The results ofimmunohistochemistry showed that there was almost no TNF-α or IL-1β expression in thehepatocytes of the control group, while the number of TNF-α-, PCNA-, andIL-1β-positive cells in the NP group was increased, with higher integral opticaldensity than the control group. Compared to the control group, the serum levels ofalanine aminotransferase, aspartate aminotransferase, triglyceride and low-densitylipoprotein in the newborn rats of the NP group were significantly increased. Therewas no significant difference in the serum level of high-density lipoprotein orcholesterol between the groups. Perinatal exposure to NP can interfere with thein vivo estrogen and progesterone levels of pregnant rats,resulting in threatened abortion, dystocia and other adverse delivery outcomes. Highliver and serum NP levels of the newborn rats led to alteration of liver tissuestructure and function. The NP-induced hepatotoxicity is probably mediated byinflammatory cytokines TNF-α and IL-1α.