Abstract：Objective To observe the effects of perinatal exposure to benzo[a]pyrene (B[a]P) on the expression of pancreatic duodenal homeobox-1 (PDX-1) and mitochondrial transcription factor A (TFAM) and mitochondrial DNA copy number in offspring mice, and to explore the role of maternal exposure to B[a]P in the pancreatic function damage of offspring mice. Methods Forty pregnant rats were randomly divided into the control group, the lowest dose group (2 μg/kg), the low dose group (200 μg/kg), medium dose group (800 μg/kg) and high dose group (1 600 μg/kg), with 8 rats in each group. From day 1 of pregnancy, each exposed group was given 0.2 mL/100 g body weight of B[a]P and corn oil mixture by gavage once a day until 3 weeks after delivery, while the control group was given the same dose of corn oil. The pancreatic tissue of three-week-old mice were collected after abdominal anesthesia for insulin immunohistochemical detection. The protein and mRNA expression levels of PDX-1 and TFAM, as well as mitochondrial DNA copy number were detected. Spearman rank correlation analysis was used to analyze the correlation between B[a]P exposure dose and the above indicators. Results The insulin-positive area ratio and average optical density of insulin in the medium and the high dose groups were significantly lower than those in the control group (all P<0.05). The insulin-positive area ratio and average optical density of insulin were negatively correlated with the B[a]P dose (rs=-0.862 and -0.858, both P<0.05). The protein expression levels of PDX-1 and TFAM in the high dose group were significantly lower than those in the control group (both P<0.05). The protein expression levels of PDX-1 and TFAM were negatively correlated with the B[a]P dose (rs=-0.756 and -0.799, both P<0.05). The mRNA expression levels of PDX-1 and mitochondrial DNA copy number in the medium and high dose groups were significantly lower than those in the control group, and the mRNA expression level of TFAM in the high dose group was significantly lower than that in the control group (all P<0.05). The mRNA expression levels of PDX-1, TFAM, and mitochondrial DNA copy number were negatively correlated with the B[a]P dose (rs=-0.722, -0.550 and -0.840, all P<0.05). Conclusion Perinatal exposure to B[a]P can induce the damage of islet β cells in offspring rats, which may be related to the decreased expression of PDX-1 and TFAM and the copy number of mitochondrial DNA.
崔蓉, 郑玉建, 鲁英, 夏力旦·阿力甫. 围产期苯并[a]芘暴露对仔鼠胰腺PDX-1、TFAM表达及线粒体DNA拷贝数的影响[J]. 预防医学, 2024, 36(1): 65-69.
CUI Rong, ZHENG Yujian, LU Ying, Xialidan Alifu. Effects of perinatal exposure to benzo[a]pyrene on the expressionof PDX-1 and TFAM in pancreas and mitochondrial DNA copynumber in offspring rats. Preventive Medicine, 2024, 36(1): 65-69.
[1] WHEELOCK K,ZHANG J J,MCCONNELL R,et al. A novel method for source-specific hemoglobin adducts of nitro-polycyclic aromatic hydrocarbons[J/OL]. Environ Sci Process Impacts,2018 [2023-11-20]. https://doi.org/10.1039/C7EM00522A. [2] ZHAO N,WU W W,CUI S W,et al. Effects of benzo[a]pyrene-DNA adducts,dietary vitamins,folate,and carotene intakes on preterm birth:a nested case-control study from the birth cohort in China[J/OL]. Environ Health,2022,21(1)[2023-11-20]. https://doi.org/10.1186/s12940-022-00859-7. [3] ZHANG Y,YANG Y H,ZHANG Q,et al.Effect of benzo[a]pyrene-DNA adduct in cord blood on the neurodevelopment of 12-month-old infants in Qingdao City[J]. Neuropsychiatr Dis Treat,2019,15:3351-3357. [4] 李珊珊. 胰岛素抵抗及高胰岛素血症促进胰腺癌发生的研究进展[J]. 预防医学,2021,33(11):1122-1125,1129. [5] OU K L,SONG J L,ZHANG S Q,et al.Prenatal exposure to a mixture of pahs causes the dysfunction of islet cells in adult male mice:association with type 1 diabetes mellitus[J/OL]. Ecotoxicol Environ Saf,2022,239 [2023-11-20]. https://doi.org/10.1016/j.ecoenv.2022.113695. [6] WANG N,TONG R,XU J,et al. PDX1 and MC4R genetic polymorphisms are associated with type 2 diabetes mellitus risk in the Chinese Han population[J/OL]. BMC Medical Genomics,2021,14[2023-11-20]. https://doi.org/10.1186/s12920-021-01037-3. [7] ŠPAČEK T,PAVLUCH V,ALÁN L,et al. Nkx6.1 decline accompanies mitochondrial DNA reduction but subtle nucleoid size decrease in pancreatic islet β-cells of diabetic Goto Kakizaki rats[J/OL]. Sci Rep,2017,7(1)[2023-11-20]. https://doi.org/10.1038/s41598-017-15958-6. [8] World Health Organization,International Programme on Chemical Safety. Selected non-heterocyclic polycyclic aromatic hydrocarbons[EB/OL].[2023-11-20]. https://iris.who.int/handle/10665/41958. [9] ALEXANDER D A,NORTHCROSS A,KARRISON T,et al.Pregnancy outcomes and ethanol cook stove intervention:a randomized-controlled trial in Ibadan,Nigeria[J]. Environ Int,2018,111:152-163. [10] 崔蓉,郑玉建,鲁英,等. 子宫内B[a]P暴露与子代鼠BPDE-DNA加合物及胰腺功能损伤的关系[J]. 预防医学,2022,34(4):335-339,345. [11] ZHANG H X Y, HAN Y Q, QIU X H,et al.Association of internal exposure to polycyclic aromatic hydrocarbons with inflammation and oxidative stress in prediabetic and healthy individuals[J/OL].Chemosphere,2020,253[2023-11-20].https://doi.org/10.1016/j.chemosphere.2020.126748. [12] CHEN J S, ZHONG L, WU J,et al.A murine pancreatic islet cell-based screening for diabetogenic environmental chemicals[J/OL]. J Vis Exp,2018,25(136)[2023-11-20].https://doi.org/10.3791/57327. [13] BREUNIG M,MERKLE J,MELZER M K,et al.Differentiation of human pluripotent stem cells into pancreatic duct-like organoids[J/OL].STAR Protoc,2021,2(4)[2023-11-20].https://doi.org/10.1016/j.xpro.2021.100913. [14] Zhang Y J,FANG X Y,WEI J H,et al.PDX-1:a promising therapeutic target to reverse diabetes[J/OL].Biomolecules,2022,12[2023-11-20].https://doi.org/10.3390/biom12121785. [15] JEZEK P,DLASKOVA A.Dynamic of mitochondrial network,cristae,and mitochondrial nucleoids in pancreatic beta-cells[J]. Mitochondrion,2019,49:245-258. [16] FAZZINI F,LAMINA C,RAFTOPOULOU A,et al.Association of mitochondrial DNA copy number with metabolic syndrome and type 2 diabetes in 14 176 individuals[J]. J Intern Med,2021,290(1):190-202. [17] KANG G G,FRANCIS N,HILL R,et al. Coloured rice phenolic extracts increase expression of genes associated with insulin secretion in rat pancreatic insulinoma beta-cells[J/OL]. Int J Mol Sci,2020,21(9)[2023-11-20]. https://doi.org/10.3390/ijms21093314. [18] YASUKAWA T,KANG D.Assessing TFAM binding to human mitochondrial DNA[J]. Methods Mol Biol,2023,26(15):139-151.
