Long-term effects of mild intrauterine hyperglycemia on glucose and lipid metabolism in intergenerational rat offspring / 中华围产医学杂志

ABSTRACT

Objective To observe the long-term effects of maternal mild hyperglycemia on the growing development and glucose and lipid metabolism in intergenerational rat offspring.Methods Streptozotocin (25 mg/kg) was administered to 14 pregnant Wistar rats intraperitoneally on the first day of gestation to induce an animal model of mild intrauterine hyperglycemia,which was successful in nine rats.Seven pregnant rats without streptozotocin intervention served as controls.Female first-generation offspring (F1) rats were intercrossed with normal male rats to obtain the second-generation offspring (F2) rats.F1 and F2 rats were divided into 8 groupsfemale group (group F1-G-♀) or male group (group F1-G-♂) exposed to intrauterine hyperglycemia;female group (group F1-C-♀) or male group (group F1-C-♂) exposed to intrauterine euglycemia;transgenerational female group (group F2-G-♀) or male group (group F2-G ♂)exposed to intrauterine hyperglycemia;and transgenerational female group (group F2-C-♀) or male group (group F2-C-♂) exposed to intrauterine euglycemia.Body weight of the offspring was recorded.At the age of 28 weeks,the weight of pancreas and visceral fat,fasting plasma glucose (FPG),fasting insulin,total triglyceride,total cholesterol,high-density lipoprotein-cholesterol,low-density lipoprotein-cholesterol were measured in all groups.Two sample t test was used for statistical analysis.Results (1) At 4,24 and 28 weeks old,the body weight of group F2-G-♀ [(177.3± 12.3),(314.5± 13.9) and (322.3± 16.2) g] was remarkably increased compared with group F2-C-♀ [(164.3±6.0),(290.2± 18.3) and (300.2± 16.2) g,t=-2.324,-2.584and-2.359,all P ＜ 0.05].(2) At 28 weeks,the pancreas weight and the ratio of pancreas weight to body weight of group F1-G-♀ [(0.53 ±0.05) g and (0.17±0.02)％] were decreased significantly compared with group F1-C-♀ [(0.65±0.04) g and (0.21±0.02)％,t=4.159 and 2.483,both P ＜ 0.05].The pancreas weight,ratio of pancreas weight to body weight,visceral fat weight and fat weight of mass ratio in groups F2-G-♂ and F2-G-♀ were not remarkably different from groups F2-C-♂ and F2-C-♀,respectively (all P ＞ 0.05).(3)The level of FPG at three weeks of age in F2-G-♀ group was higher than in F2-C-♀ group [(6.5±0.8) vs (4.9±1.2) mmol/L,t=-2.786,P ＜ 0.05],and it was also higher in F2-G-♂ group than in F2-C-♂ group [(6.3±0.8) vs (4.7± 1.0) mmol/L,t=-2.696,P ＜ 0.05].At 28 weeks,the FPG level was (6.7±0.6) and (8.4±2.2) mmol/L in F2-G-♀ and F2-G-♂ groups,being higher than in F2-C-♀ and F2-C-♂ groups,respectively [(5.8±0.5) and (6.2± 1.0) mmol/L,t=-2.695 and-2.337,both P ＜ 0.05].Compared with F1-C-♀ group [(0.61 ±0.10) mmol/L],the high-density lipoprotein-cholesterol level was lower in F1-G-♀ group [(0.47±0.05) mmol/L,t=2.433,P ＜ 0.05].(4) In groups F1-G-♀,F2-G-♀ and F2-G-♂,the structure of the islet cells was obviously atrophic and disordered,and β-cells were slightly decreased and distributed unevenly,but group F1-G-♂ had significantly increased β-cells with hypertrophic islet size compared with control group.Conclusions F 1 rat offsprings exposed to mild intrauterine hyperglycemia experience excessive weight gain after birth,impaired structure of the islet,metabolic abnormality,increased visceral fat weight and glucose and lipid metabolism disorder,which show intergenerational inheritance and gender differences.