Effects And Mechanisms Of 2,2’,4,4’-Tetrabromodiphenyl Ether Exposure On Body Weight,Adipokine And Insulin Sensitivity Of Offspring In Pregnant Mice

Objective: An animal model of 2,2?,4,4?-Tetrabromodiphenyl ether(BDE-47)during pregnant mice was established to explore the effects and mechanisms of BDE-47 exposure on body weight,adipokine,and insulin sensitivity of offspring in pregnant mice.Methods: 20 healthy SPF C57BL/6 female mice were randomly divided into 4 groups according to body weight: control group,BDE-47 high-dose group,BDE-47 medium-dose group,and BDE-47 low-dose group.After the female mice acclimatized for 1 week,they were caged with SPF grade healthy C57BL/6 male mice.On the first day of successful closure of the cages,the female mice were administrated with gavage for 10 days.1 week after the exposure,female mice were injected intraperitoneally glucose tolerance test(IPGTT).6 weeks after the birth of the offspring,the female mice and offspring were anesthetized,the eyeballs were collected for blood collection,and tissues were collected for follow-up research: ELISA was used to determine the levels of Insulin,Leptin,and Adiponectin in the serum of mice;qRT-PCR and Western Blot method was used to measure the mRNA and protein expression levels of PPARγ,Leptin and Adiponectin genes in mouse liver tissue.Results: 1.Change in body weight: The weight of the mice was recorded on the 15 th day of birth,3 times a week,and compared every other week.On the 15 th and 22 nd days,the weight of the female mice in the BDE-47-exposed group was higher than that of the control female mice,On the 15 th day,the weight of the male mice was higher than that of the control male mice(P<0.05).2.Liver and kidney weights and organ coefficients: The liver weight and organ coefficients of female mice in each BDE-47 exposure group were increased compared with the control group(P<0.05);The liver weight and organ coefficients of the mice in the group were larger than those in the control group(P<0.05).3.female mice IPGTT: The blood glucose level in the high-dose group 30 minutes after abdominal glucose loading was significantly lower than the control group(P<0.05);The area under the overall blood glucose curve of mice in each group showed a continuous decrease trend with the increase of BDE-47 dose.4.female mice ELISA: The serum insulin levels in the high-dose group were significantly higher than those in the other groups(P<0.05).The serum leptin levels in the high-dose and middle-dose groups were higher than those in the control group(P<0.05).5.qRT-PCR and Western blot: Female mice: the mRNA and protein expressions of PPARγ and leptin genes in the liver tissues of high-dose groups decreased,while the mRNA expression of adiponectin genes increased(P<0.05);the PPARγ gene protein expression in the liver tissues of the female mice in the middle dose group decreased,and the mRNA and protein expression of the Leptin gene and Adiponectin gene decreased(P<0.05);the PPARγ gene protein expression in the liver tissues of the female mice in the low-dose group decreased,and the mRNA expression of Adiponectin gene was decreased(P<0.05).Female offspring: the mRNA and protein expression of PPARγ gene in the liver tissues of female offspring in the high-dose group decreased,and the mRNA expression of the Leptin gene and Adiponectin gene increased(P(27)0.05);the mRNA expression of PPARγ gene and Adiponectin gene in the liver tissues of female offspring in the middle dose group decreased(P(27)0.05);the mRNA expression of PPARγ gene was decreased in female offspring liver tissues of low-dose groups,and the expression of Adiponectin gene protein was increased(P(27)0.05).Male offspring: the mRNA and protein expression of PPARγ gene in the liver tissues of male offspring in the high-dose group increased(P(27)0.05);the mRNA expression of Leptin gene in liver tissues of male offspring in the high-dose group increased(P(27)0.05);the mRNA and protein expression level of Adiponectin gene in the liver tissues of male offspring in the low-dose group decreased(P(27)0.05).Conclusion: 1.BDE-47 exposure during pregnancy can cause the offspring mice to gain weight during early postnatal development and affect liver and kidney organ weights of female mice and offspring.2.BDE-47 exposure during pregnancy can cause: Decreased mRNA and protein expression of PPARγ,leptin and adiponectin genes in female mice;Decreased mRNA and protein expression of PPARγ and adiponectin genes in female offspring;Increased mRNA expression and protein expression of PPARγ gene in male offspring,decreased expression and mRNA expression of adiponectin gene in male offspring.This may be one of the mechanisms by which BDE-47 regulates adipokines secreted by adipocytes and affects insulin sensitivity.