Transmaternal Bisphenol A Exposure Accelerates Diabetes Type 1 Development in NOD Mice
Transmaternal Bisphenol A Exposure Accelerates Diabetes Type 1 Development in NOD Mice
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DOI：
10.1093/toxsci/kft242
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发表时间：
2014-02-01
影响因子：
3.8
通讯作者：
Nygaard, Unni Cecilie
中科院分区：
文献类型：
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作者：
Bodin, Johanna;Bolling, Anette Kocbach;Nygaard, Unni Cecilie
1 型糖尿病是一种具有遗传倾向的自身免疫性疾病，由生命早期的环境因素引发。流行病学研究表明，在所有分析的人类尿液样本中，约 90% 都检测到了双酚 A (BPA)（一种内分泌干扰物）。在这项研究中，发现雌性非肥胖糖尿病 (NOD) 小鼠通过母体饮用水（0、0.1、1 和 10 毫克/升）接触 BPA 后，会增加其后代的胰岛素炎严重程度和糖尿病发病率。与对照组相比，最高暴露组的雌性后代在 11 周龄时胰岛炎的严重程度和 20 周时的糖尿病患病率均显着增加。在经母体暴露的后代发生胰岛炎之前，在胰岛中观察到凋亡细胞数量增加、组织驻留巨噬细胞减少和调节性 T 细胞增加。可检测到的凋亡细胞被鉴定为主要是产生胰高血糖素的α细胞，但也有组织驻留的巨噬细胞和β细胞。在局部（胰腺）淋巴结中，调节性 T 细胞和 NKT 细胞群均不受母体 BPA 暴露的影响。母体 BPA 暴露可能引起后代的全身免疫变化，LPS 和 ConA 诱导的脾细胞细胞因子分泌的变化证明了这一点。总之，在子宫内和哺乳期经母体接触 BPA 会加速 NOD 小鼠自发性糖尿病的发展。这种加速似乎与生命早期对免疫系统的调节作用有关，从而导致生命后期的不利影响。
Diabetes mellitus type 1 is an autoimmune disease with a genetic predisposition that is triggered by environmental factors during early life. Epidemiological studies show that bisphenol A (BPA), an endocrine disruptor, has been detected in about 90% of all analyzed human urine samples. In this study, BPA was found to increase the severity of insulitis and the incidence of diabetes in female non obese diabetic (NOD) mice offspring after transmaternal exposure through the dams drinking water (0, 0.1, 1, and 10mg/l). Both the severity of insulitis in the pancreatic islets at 11 weeks of age and the diabetes prevalence at 20 weeks were significantly increased for female offspring in the highest exposure group compared to the control group. Increased numbers of apoptotic cells, a reduction in tissue resident macrophages and an increase in regulatory T cells were observed in islets prior to insulitis development in transmaternally exposed offspring. The detectable apoptotic cells were identified as mostly glucagon producing alpha-cells but also tissue resident macrophages and beta-cells. In the local (pancreatic) lymph node neither regulatory T cell nor NKT cell populations were affected by maternal BPA exposure. Maternal BPA exposure may have induced systemic immune changes in offspring, as evidenced by alterations in LPS- and ConA-induced cytokine secretion in splenocytes. In conclusion, transmaternal BPA exposure, in utero and through lactation, accelerated the spontaneous diabetes development in NOD mice. This acceleration appeared to be related to early life modulatory effects on the immune system, resulting in adverse effects later in life.