Effects Of Maternal Endotoxin Exposure During Pregnancy On Glucose Metabolism In The Male Offspring At Different Life Stages

Background Extensive epidemiological studies and animal experiments demonstrated that adverse events early in development,particularly during intrauterine life,may result in permanent changes to the structure and function of the infant organs through a variety of mechanisms,which lead to the related fetal diseases(diabetes)in later life.Therefore,the present study investigated the pathogenesis of diabetes from the perspective of intrauterine adverse environment,which is conducive to pregnancy care,reasonable nutrition and behavior of pregnant women,early identification of pregnant women at high risk,targeted treatment programs to avoid fetal exposure to an unfavorable intrauterine environment.Previous studies have confirmed that maternal endotoxin(lipopolysaccharide,LPS)exposure during pregnancy is one of the factors that cannot be ignored during pregnancy,which lead to glucose metabolism disorders in the male offspring,while no significant effect was observed between female LPS offspring and female control offspring.However,the underlying mechanism of glucose metabolism disorder induced by maternal LPS exposure during pregnancy in the male offspring is not clear yet.Objective Based on our previous study in which maternal LPS exposure during pregnancy resulted in glucose metabolism disorder in the male offspring,the present study investigated the effects of LPS exposure on the levels of endogenous sex hormones,sex hormone receptor levels and metabolizing enzyme(aromatase)of liver and adipose tissues in the male offspring at different life stages,to clarify the underlying mechanism of glucose metabolism disorder induced by maternal LPS exposure during pregnancy in the male offspring.Methods To clarify the effect of maternal LPS exposure during pregnancy on glucose metabolism in the male offspring,the pregnant mice were randomly divided into two groups,LPS group and control group.The LPS mice were intraperitoneally injected with LPS(50 ?g / kg /d)from gestational day(GD)15 to GD17.The control mice were injected with saline.The pregnant mice were fed with standard chow diets.At weaning,the male mice were divided into two groups as follows,Control group and LPS group.Glucose tolerance test(GTT)and insulin tolerance test(ITT)were assessed at postnatal day(PND)60 and PND120.At different life stages(PND14: juvenile;PND35: adolescence;PND60: adulthood and PND120: middle-aged),the male offspring were sacrificed after fasting for 12 h,respectively.Blood was collected for fasting blood glucose,insulin,T,E2,and the T / E2 ratio was calculated.Liver tissues were collected to measure protein and m RNA levels of sex hormone receptor and aromatase.Adipose tissue was collected to measure protein and m RNA levels of aromatase.In addition,insulin sensitivity test was conducted in the male offspring at PND120 to observe the level of insulin signaling.Results Maternal LPS exposure during pregnancy induced glucose intolerance and insulin resistance in the male offspring at middle age.Maternal LPS exposure increased fasting blood glucose and decreased serum insulin levels.Moreover,maternal LPS exposure during pregnancy decreased hepatic phosphorylated(p)-AKT/AKT ratio and hepatic insulin signaling levels(IRS1,IRS2).In addition,maternal LPS exposure during pregnancy significantly decreased the serum T / E ratio in the male offspring from adolescence to middle age;maternal LPS exposure during pregnancy significantly increased the expression of hepatic ER? and hepatic ER? in the male offspring from adolescence to middle age.Maternal LPS exposure during pregnancy reduced hepatic AR from adolescence to adulthood.Maternal LPS exposure during pregnancy increased serum E2 level and reduced serum T level at adulthood.Maternal LPS exposure during pregnancy increased serum E2 level in the male offspring at middle age.Maternal LPS exposure during pregnancy upregulated hepatic aromatase levels in the male offspring at all phases of development.Maternal LPS exposure upregulated aromatase levels of adipose tissue at PND120 in the male offspring.Conclusion Maternal LPS exposure upregulated aromatase expressions,followed by a reduction in the T/E2 ratio and an alteration in sex hormone receptor activity,which might be involved in the development of glucose metabolism disorders in middle-aged male offspring.