Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1289/EHP1674 |
Sex- and Dose-Specific Effects of Maternal Bisphenol A Exposure on Pancreatic Islets of First- and Second-Generation Adult Mice Offspring | |
Bansal, Amita1,2,3; Rashid, Cetewayo1,2,3; Xin, Frances2,4; Li, Changhong5; Polyak, Erzsebet6; Duemler, Anna1,7; van der Meer, Tom1,8; Stefaniak, Martha4; Wajid, Sana9; Doliba, Nicolai10; Bartolomei, Marisa S.1,2,4; Simmons, Rebecca A.1,2,3 | |
2017-09-01 | |
发表期刊 | ENVIRONMENTAL HEALTH PERSPECTIVES
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ISSN | 0091-6765 |
EISSN | 1552-9924 |
出版年 | 2017 |
卷号 | 125期号:9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Netherlands |
英文摘要 | BACKGROUND: Exposure to the environmental endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with the increased risk of diabetes and obesity. However, the underlying mechanisms remain unknown. We recently demonstrated that perinatal BPA exposure is associated with higher body fat, impaired glucose tolerance, and reduced insulin secretion in first- (F1) and second-generation (F2) C57BL/6J male mice offspring. OBJECTIVE: We sought to determine the multigenerational effects of maternal bisphenol A exposure on mouse pancreatic islets. METHODS: Cellular and molecular mechanisms underlying these persistent changes were determined in F1 and F2 adult offspring of F0 mothers exposed to two relevant human exposure levels of BPA (10 mu g/kg/d-LowerB and 10 mg/kg/d-UpperB). RESULTS: Both doses of BM significantly impaired insulin secretion in male but not female F1 and F2 offspring. Surprisingly, LowerB and-UpperB induced islet inflammation in male 1 offspring that persisted into the next generation. We also observed close-specific effects of BPA on islets in males. UpperB exposure impaired mitochondrial function, whereas LowerB exposure significantly reduced beta-cell mass and increased beta-cell death that persisted in the F2 generation. Transcriptome analyses supported these physiologic findings and there were significant dose-specific changes in the expression of genes regulating inflammation and mitochondrial function. Previously we observed increased expression of the critically important beta-cell gene, Igf2 in whole F1 embryos. Surprisingly, increased Igf2 expression persisted in the islets of male F1 and F2 offspring and was associated with altered DNA methylation. CONCLUSION: These findings demonstrate that maternal BPA exposure has dose- and sex-specific effects on pancreatic islets of adult F1 and F2 mice offspring. The transmission of these changes across multiple generations may involve either mitochondrial dysfunction and/or epigenetic modifications. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000461478500002 |
WOS关键词 | ESTROGEN-RECEPTOR-ALPHA ; BETA-CELL MASS ; GROWTH-FACTOR-II ; MESSENGER-RIBONUCLEIC-ACID ; MITOCHONDRIAL DYSFUNCTION ; DEVELOPMENTAL EXPOSURE ; EPIGENETIC DISRUPTION ; GLUCOSE-HOMEOSTASIS ; PERINATAL EXPOSURE ; INSULIN-SECRETION |
WOS类目 | Environmental Sciences ; Public, Environmental & Occupational Health ; Toxicology |
WOS研究方向 | Environmental Sciences & Ecology ; Public, Environmental & Occupational Health ; Toxicology |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/23083 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Penn, Ctr Res Reprod & Womens Hlth, Perelman Sch Med, 1308 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA; 2.Univ Penn, Ctr Excellence Environm Toxicol, Perelman Sch Med, Philadelphia, PA 19104 USA; 3.Childrens Hosp Philadelphia, Div Neonatol, Philadelphia, PA 19104 USA; 4.Univ Penn, Epigenet Inst, Dept Cell & Dev Biol, Perelman Sch Med, Philadelphia, PA 19104 USA; 5.Childrens Hosp Philadelphia, Dept Pediat, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA; 6.Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA; 7.Penn State Univ, Eberly Coll Sci, University Pk, PA 16802 USA; 8.Univ Groningen, Dept Pediat, Groningen, Netherlands; 9.Univ Penn, Perelman Sch Med, Exposure Biol Informat Core, Philadelphia, PA 19104 USA; 10.Univ Penn, Dept Biochem & Biophys, Perelman Sch Med, Philadelphia, PA 19104 USA |
推荐引用方式 GB/T 7714 | Bansal, Amita,Rashid, Cetewayo,Xin, Frances,et al. Sex- and Dose-Specific Effects of Maternal Bisphenol A Exposure on Pancreatic Islets of First- and Second-Generation Adult Mice Offspring[J]. ENVIRONMENTAL HEALTH PERSPECTIVES,2017,125(9). |
APA | Bansal, Amita.,Rashid, Cetewayo.,Xin, Frances.,Li, Changhong.,Polyak, Erzsebet.,...&Simmons, Rebecca A..(2017).Sex- and Dose-Specific Effects of Maternal Bisphenol A Exposure on Pancreatic Islets of First- and Second-Generation Adult Mice Offspring.ENVIRONMENTAL HEALTH PERSPECTIVES,125(9). |
MLA | Bansal, Amita,et al."Sex- and Dose-Specific Effects of Maternal Bisphenol A Exposure on Pancreatic Islets of First- and Second-Generation Adult Mice Offspring".ENVIRONMENTAL HEALTH PERSPECTIVES 125.9(2017). |
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