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Toxicol Lett. 2016 Mar 14;245:59-67. doi: 10.1016/j.toxlet.2016.01.007. Epub 2016 Jan 15.

Insulin signaling disruption in male mice due to perinatal bisphenol A exposure: Role of insulin signaling in the brain.

Author information

1
Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing 211166, China.
2
Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing 211166, China; Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210000, China.
3
Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing 211166, China. Electronic address: wangjun@njmu.edu.cn.
4
Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing 211166, China. Electronic address: hxiao@njmu.edu.cn.

Abstract

Bisphenol A (BPA), an environmental estrogenic endocrine disruptor, is widely used for producing polycarbonate plastics and epoxy resins. Available data have shown that perinatal exposure to BPA contributes to peripheral insulin resistance, while in the present study, we aimed to investigate the effects of perinatal BPA exposure on insulin signaling and glucose transport in the cortex of offspring mice. The pregnant mice were administrated either vehicle or BPA (100 μg/kg/day) at three perinatal stages. Stage I: from day 6 of gestation until parturition (P6-PND0 fetus exposure); Stage II: from lactation until delactation (PND0-PND21 newborn exposure) and Stage III: from day 6 of pregnancy until delactation (P6-PND21 fetus and newborn exposure). At 8 months of age for the offspring mice, the insulin signaling pathways and glucose transporters (GLUTs) were detected. Our data indicated that the insulin signaling including insulin, phosphorylated insulin receptor (IR), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular signal regulated protein kinase (p-ERK) were significantly decreased in the brain. In parallel, GLUTs (GLUT1/3/4) were obviously decreased as well in BPA-treated group in mice brain. Noteworthily, the phosphorylated tau (p-tau) and amyloid precursor protein (APP) were markedly up-regulated in all BPA-treated groups. These results, taken together, suggest the adverse effects of BPA on insulin signaling and GLUTs, which might subsequently contribute to the increment of p-tau and APP in the brain of adult offspring. Therefore, perinatal BPA exposure might be a risk factor for the long-term neurodegenerative changes in offspring male mice.

KEYWORDS:

Amyloid precursor protein; Bisphenol A; Brain insulin signaling; Glucose transporter; Tau

PMID:
26779933
DOI:
10.1016/j.toxlet.2016.01.007
[Indexed for MEDLINE]

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