Effects And Mechanism Of Prenatal Exposure To PCB118 During On Body Weight And Islet Function In Offspring Rats

BackgroundDiabetes(DM)is a metabolic disorder characterized by chronic hyperglycemia caused by multiple factors.Because of a variety of acute and chronic complications,DM has an adverse impact on the quality of life of patients,consuming a large number of national medical resources.Chinese ancient medicine has a very early understanding of diabetes,called diabetes as Xiaokebing.During Spring and Autumn Period,there is a systematic description on the etiology,pathogenesis,diagnosis and treatment of diabetes and so on in the Huangdi Neijing.Polychlorinated biphenyls(PCBs)are endocrine disrupter chemicals.There are a variety of chlorine atoms in biphenyl chlorine compounds collectively,mainly through the food chain in the human body,often detected in milk,urine.Human is exposed to PCBs through ingestion,inhalation,skin contact,placental permeability and breastfeeding,present in the body's adipose tissue for a long time.In the 1930s,scholars observed that embryonic and juvenile growth environments may have an impact on their adult health status.Type 2 diabetes,in addition to polygenetic susceptibility and environmental factors,a lot of studies have shown that there is association between the nutritional status of pregnancy,birth weight and adult islet function,blood glucose levels,obesity and insulin sensitivity,called fetal source adult disease(FOAD)or "Barker doctrine".Embryo or infancy,because DNA repair function,liver detoxification and metabolic function are not perfect,therefore,is more sensitive to PCBs.compared with adulthood.Perinatal exposure to PCBs can have more serious adverse consequences,and may be manifested in adulthood.Therefore,to prevent and early interfere in adult chronic diseases,it is important for prevention and treatment of diabetes to pay attention to the factors affecting the development of embryos during pregnancy.Part1Objective To observe the effects of prenatal exposure to PCB118 on the birth weight,growth,development of pancreatic islets and insulin sensitivity in different age of offspring rats.MethodsIn this study,SD rats were used to study the effects of corn oil(control group),10?g/kg/d(about 0.2 times of the breast milk content),100?g/kg/d,500?g/kg/d PCB118 concentration in the middle of gestation(gestation 11-17 days of pregnancy)through gavage.Birth weight,growth curve,blood glucose,insulin and oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were carried out to compare between different groups.OGTT and ITT were performed at weaning,8 and 27 weeks,respectively.ResultsThe birth weight of the exposed group was significantly lower than that of the control group,however,the catch-up growth pattern was found during the growth process in exposed group.Male offspring showed in weaning early phase of insulin secretion was obviously decreased and in adulthood glucose tolerance was impaired and insulin sensitivity decreased,while female offspring mainly showed impaired glucose tolerance in the high-dose group.ConclusionPrenatal exposure to PCB118 can lead to low birth weight and catch up growth in offspring rats,undermine the islet function and then cause glucose metabolism disorders,more obviously in male offspring.Part 2ObjectiveTo observe the effects of prenatal exposure to PCB118 on the expression of insulin-related genes,apoptosis-related genes in the offspring rats and islet cell morphology and explore the possible mechanism of glucose metabolism disorders.MethodsAnimal models were the same as the first part.Analysis of morphology and quality of islet cells in 27th week were carried out by HE and immunofluorescence double staining.The glucose-stimulated insulin secretion test(GSIS)in isolated adult islet cells was used to analyze their function in vitro.RT-PCR was used to compare the mRNA expression of PDX-1,Maf A and Insulin in experimental group and control group.The mRNA expression of bax,bcl-2 and Caspase-3 of pancreatic tissue in 27th week was also analyzed.ResultsCompared with control group,the masses of islet cell of adult male offspring rats were reduced using HE and immunofluorescence double staining.GSIS showed a significant decrease of ? cell function in male offspring,and female offspring were impaired only in high dose exposure group.Compared with control group,the mRNA expression of PDX-1,Maf A and insulin was decreased in male experimental groups,and the expression of PDX-1,Maf A and insulin in the high dose group was lower than that in control.The ratio of bax/bcl-2 was up-regulated in adult offspring.The mRNA expression of Caspase-3 in male experimental groups and female high-dose was up-regulated.ConclusionPrenatal exposure to PCB118 can lead to impaired pancreatic ? cell function and glucose metabolism disorders,which may be attributed to ? islet cell apoptosis increase.