| Background A growing body of research is now concerned with the possible role of early life events in the development of disease risk in later human life.In 2003,Barker put forward the theory of Doha.Doha(developmental origins of health and disease,DOHa D),the origin of health and disease development,is a new medical concept proposed by a large number of epidemiological studies in recent years on the origin of human diseases.The theory suggests that humans in early life(fetal,infant,childhood)this key stage exposed to any adverse factors may affect the fetus,infant developmental plasticity,bring the phenotype changes of tissues and organs occur permanent or procedural changes in the structure and function of the final.In future a series of childhood development origin of adult diseases,including metabolic diseases,cardiovascular disease,cancer,birth defects,mental and behavior disorders and other chronic non communicable diseases(NCD)occurrence and development.There are 4 periods in early life that may be the sensitive window for the origin of long-term diseases,including gametogenesis,zygote formation,intrauterine development and puberty.In the early life of many adverse exposure,tobacco is an important and common adverse factor in early life of offspring.Epidemiological findings suggest that smoking before fathers may lead to overweight and obesity when male offspring are born.Father smoking can be genetic chronic disease to the next generation,offspring of endocrine disorders,obesity,suffering from metabolic diseases and mentaldisorders,the probability of occurrence of cancer may increase.In the early stage of life,maternal unilateral pregnancy exposure to tobacco can lead to miscarriage during pregnancy,higher perinatal mortality,lower birth weight,premature birth,and intrauterine growth restriction.Women who smoke during pregnancy can lead to overweight or even obesity later in life.Some animal studies have found that perinatal exposure to nicotine is an important pathway to the pathophysiology of diabetes in the offspring,including reduced beta cell volume and impaired beta cell function.In the early stage of life,parental dual tobacco exposure may be associated with an increased risk of overweight in childhood.Offspring of parents who smoke at the same time,women have an increased risk of puberty and adult weight gain.In order to clarify the early life exposure to tobacco caused by parental offspring fetal derived metabolic disease specific period(gamete formation,zygote formation stage,intrauterine growth period),we established an animal model of early life exposure to tobacco induced offspring parent fetal origins of diabetes,which gave us a lot of inspiration,will undoubtedly provide a new the window for exploring the etiology and intervention of chronic diseases for future generations,formulate strict tobacco control plan and vigorously promote eugenics provides a theoretical basis for.Objective According to the results of epidemiological studies on human,the use of C57 mice through parental cigarette smoking condensate(CSC)was established in early life exposure to tobacco animal model of elicitors generation in diabetic rats,clear early life exposure to tobacco parental effects on offspring metabolic diseases,determine the life to play the role of early tobacco sensitive window period.To understand the influence of early tobacco exposure on the growth and development of offspring in early life.Methods 1)paternal C57 mice CSC exposure treatment(gamete formation stage): C57BL/6J wild-type male rats,from 4 weeks old,continuous feeding cigarette smoke concentrate CSC(2mg/m L,change the next day).Cigarette smoke concentration(CSC)male parent exposure group;2)paternal C57 mice normal treatment(gamete formation stage): another group of C57BL/6J wild type male mice from 4 weeks old normal feeding,as a control group.3)female C57 mice exposed to CSC treatment(zygote formation period and intrauterine growth period): the wild type C57BL/6J female rats on February at the age of-6 months of the estrous cycle in female rats vaginal smear to detect estrus,female rats and male CSC rats and control group rats according to the proportion of 1:1 cage.Second days,vaginal smears,vaginal plugs or vaginal smears revealed that the male sperm was determined to be fertilized,and the day was 0.5 days.From the 0.5 day of gestation,a group of female rats were continuously fed CSC(2mg/m L,changed every other day)to 18.5 days to weigh and take out a single cage rearing.4)female mice C57 mice normal treatment(zygote formation and intrauterine growth),a group of female rats see plug or sperm,after normal rearing to 18.5 days,weighing and take out a single cage rearing.5)the four groups of animal models: 1 x 2 female male;female CSC male and female male x x;CSC;the male female CSC x CSC;6)four group rats,blood glucose and blood lipid related indicators detection: the four groups were the offspring of growth to 4 weeks and 8 weeks of tail vein blood for OGTT detection(detection time point for fasting blood glucose,rats by intraperitoneal injection of glucose after experimental dose 30,60,90 and 120min;four groups of blood glucose levels)rat growth to fourth weeks and 8 weeks using the collected serum lipids(cholesterol and triglyceride)detection;four pups at postnatal day samples of muscle biopsy for lower limb specimens for fat cells;7)the four groups of rats were collected at fourth weeks and 8 weeks after birth to collect the genomic DNA and analyze the sequence of 16SV4 to understand the relationship between microbial flora and blood glucose and blood lipids.8)the growth and development indexes of four groups were detected,and the body weight and morphological development of the four groups were recorded at 14.5 days after birth.The weight gain at birth and after birth was recorded,and the growth curve was drawn up to eighth weeks.9)understand the four groups of pregnant rats: pregnancy course and outcome of pregnancy records(pregnant 0.5 days to 18.5 days gestation)four groups of maternal weight gain increased;the number of litter delivery;delivery time.Result 1 metabolism of each offspring rats,we detected the representative metabolic indexes,blood sugar and blood lipid in each group at fourth and 8 weeks of puberty and sexual maturity respectively.The results showed that there were abnormal glucose metabolism at the fourth week and the 8 week,and the level of blood sugar increased obviously,and reached the diagnostic standard of diabetes mellitus Abnormally elevated serum lipids reached the diagnostic criteria for hyperlipidemia,It is worth noting that the offspring of rats with normal control group have higher body weight in addition to the stages of growth and development during the day of birth.2 in the four group,a total of 97 cases of animal model,double parent tobacco exposure group had 5 cases,single female pregnancy tobacco exposure group and single parent before tobacco exposure group were found in 2 cases and 3 cases of lower limb muscles in neonatal rats with abnormal deposition of fat.3 rats in each group fourth weeks after birth,intestinal microbial exposure to tobacco group: Double parent offspring group than Bacteroides Firmicutes decreased the proportion in verrucomicrobia(Verrucomicrobia)a rapid decrease in the proportion of Proteobacteria(Proteobacteria)abundance increased,with statistical difference Biomarker and Proteobacteria(Proteobacteria).Rats in each group eighth weeks after birth and 4 weeks: the intestinal microflora of rats,compared with normal control group,the parent of double exposure to tobacco group,simple group and single female parent tobacco exposure index of tobacco exposure group Alpha diversity are declining,the parents double tobacco exposure group was the most obvious,this shows that the diversity of these three groups of species is decreased,the parents double exposure to tobacco group even.4 during the gestation period of four groups of female rats,we also studied the growth and development of the four groups of female rats at 14.5 days gestation.Fourgroups of fetal rats appeared during pregnancy and differences in body weight of 14.5 days,the result is compared with the normal control group,the parent of double exposure to tobacco group and single parent tobacco exposure group fetal body weight decreased significantly,and the only male tobacco exposure group compared with the normal control group did not show significant weight loss.Compared with the normal control group,the parents double tobacco exposed group and the pure maternal tobacco exposed group were significantly increased in first weeks,second weeks and 3 weeks after birth.Compared with normal control group,simple paternal exposure to tobacco group rats from first weeks to sixth weeks body weight was significantly reduced,the difference was statistically significant,reflecting the influence of parental tobacco exposure,rats in each group at different growth from birth to eighth weeks of change stages of postnatal development.5 during pregnancy,although parents double exposure to tobacco group weight gain during pregnancy degree decreased,litter amount was also slightly reduced,but these changes were not statistically significant,the four groups of female rats during pregnancy and birth weight increased the number of close to.The four groups of pregnant mice were basically the same in the number of days of production,all in the normal production period(19-21 days)production,and did not appear premature or overdue birth and other abnormalities.Conclusion 1.Early life,paternal,pre pregnancy and maternal pregnancy,while cigarette and tobacco exposure induced offspring diabetes in offspring.2 in the early stage of life,paternal,prenatal and maternal pregnancy cigarettes and tobacco exposure may affect intestinal microflora in offspring of fourth and 8 weeks,which may be related to dyslipidemia and blood glucose metabolism.3 the early life of parents exposed to tobacco does not affect the pregnancy related indicators,such as weight gain during pregnancy,litter size,pregnancy days and so on 4 early life paternal and maternal pre pregnancy and pregnancy cigarette tobacco exposure and simple maternal pregnancy cigarette tobacco exposure can lead to fetal rats in pregnancy and birth weight decreased significantly,while only paternal preexposure group had no obvious effect on body weight in late pregnancy on fetal rat sound shadow. |
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