Effects Of Intrauterine Chronic Hypoxia On Pancreatic Islet Function Of Adult Offspring Rats

Objective: To study the effects of intrauterine chronic hypoxia on pancreatic islet function in adult offspring rats,and to explore its mechanism.Methods: Twenty SD rats were randomly divided into normal control group(NC group,10 rats)and intrauterine chronic hypoxia group(ICH group,10 rats).Rats of ICH group were placed in hypoxic cells with oxygen concentration of 12 ± 1%,twice a day and each for 4 hours,for hypoxia treatment from pregnant day 7 to day21.One male offspring rat of each nest was randomly selected at 16 weeks of age for study.The pancreas were removed.HE stainings were performed for islet morphology study.IPP image analysis software were used to measure the islet area.Immunohistochemistry stainings were used to detect insulin,GK,and Glut2 expression.The expressions of insulin / Fox O1 / Pdx1 / Maf A m RNA were detected by q RT-PCR.Results:1.Compared with NC group,the body weight of ICH group was significantly lower than that of normal group at 12 hours after birth,and the difference was statistically significant(t= 23.221,P<0.05).There was no significant difference in bodyweight between the two groups(P> 0.05)2.The shapes of pancreas islets of ICH adult male rats were irregular.The distribution of cells were uneven.The islet area decreased significantly compared with NC group(11904±1573?m2 vs 15324±761?m2,P<0.05).3.Immunohistochemistry staining showed that the area of ?-cells of ICH rats was smaller than that of controls(0.85±0.10% vs 1.13±0.05,P<0.05).Insulin expression(1.50±0.51 vs 2.27±0.28,P<0.05),GK expression(3.15±0.19 vs5.47±0.33,P<0.05)and Glut2 expression(2.14±0.15 vs 3.81±0.11,P<0.05)of ICH rats were lower than that of NC rats.4.QRT-PCR showed that There was no significant difference in the relative quality expression of Fox O1 gene between ICH group and NC group.The relative quality expression of Pdx-1 gene was higher than that of NC group(1.96±0.32,P<0.05),The relative quality expression of Maf A gene was higher than that of NC group(4.32±1.12,P<0.05)and the relative quality expression of Insulin gene was higher than that of NC group(2.25±0.61,P <0.05)respectively.Conclusion: Intrauterine chronic hypoxia can induce abnormal islet morphology,islet area and beta cell area in the pancreas of offspring male rats.However,the relative expression of Maf A/Pdx-1 genes increase significantly.It is suggested that the pancreas may coexist with injury and repair under the condition.