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首页> 外文期刊>Toxicology Letters: An International Journal Providing a Forum for Original and Pertinent Contributions in Toxicology Research >Caffeine-induced fetal rat over-exposure to maternal glucocorticoid and histone methylation of liver IGF-1 might cause skeletal growth retardation
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Caffeine-induced fetal rat over-exposure to maternal glucocorticoid and histone methylation of liver IGF-1 might cause skeletal growth retardation

机译：咖啡因诱导的胎鼠过度暴露于母体糖皮质激素和肝脏IGF-1的组蛋白甲基化可能导致骨骼发育迟缓

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Several epidemiological investigations, including previous work by our laboratory, indicate that maternal caffeine consumption is associated with intrauterine growth retardation and impaired fetal length growth. Skeletal development is critical for length growth. In the present study, our goals were to determine the effects of prenatal caffeine exposures on fetal skeletal growth and to investigate the mechanisms associated with such effects. Pregnant Wistar rats were injected intragastrically with 120. mg/kg of caffeine intragastrically each day from gestational days 11-20. Maternal prenatal caffeine exposure was associated with decreased fetal femur lengths and inhibited of synthesis of extracellular matrices in fetal growth plates Moreover, caffeine exposure significantly increased the levels of fetal blood corticosterone and decreased IGF-1mRNA expression levels in the liver and growth plate. The expression levels of IGF-1 signaling pathway components (IGF-1R, IRS-1, AKT1/2 and Col2A1) were also reduced. In addition, the results of chromatin immunoprecipitation assays indicated that caffeine exposure down-regulated histone methylation of fetal IGF-1 in the liver. These results suggest that prenatal caffeine exposure may inhibit fetal skeletal growth through a mechanism that is associated with increased fetal exposure to maternal glucocorticoids and results in lower IGF-1 signaling pathway activity. Taken together, these results raise important concerns regarding the skeletal growth toxicity of caffeine and potentially indicate the intrauterine origins of adult osteoporosis and osteoarthritis.
机译：几项流行病学调查（包括我们实验室先前的工作）表明，母体咖啡因的摄入与子宫内生长迟缓和胎儿身长增长受损有关。骨骼发育对于长度增长至关重要。在本研究中，我们的目标是确定产前咖啡因暴露对胎儿骨骼生长的影响并研究与这种影响相关的机制。从妊娠第11-20天每天腹腔注射120. mg / kg咖啡因的孕妇Wistar大鼠。孕妇产前咖啡因暴露与胎儿股骨长度减少和胎儿生长板中细胞外基质合成的抑制有关。此外，咖啡因暴露显着增加胎儿血皮质酮水平，并降低肝脏和生长板中IGF-1mRNA表达水平。 IGF-1信号通路成分（IGF-1R，IRS-1，AKT1 / 2和Col2A1）的表达水平也降低了。此外，染色质免疫沉淀试验的结果表明，咖啡因暴露下调了肝脏中胎儿IGF-1的组蛋白甲基化。这些结果表明，产前咖啡因暴露可能通过与胎儿增加与孕妇糖皮质激素的暴露相关的机制抑制胎儿骨骼生长，并导致较低的IGF-1信号通路活性。综上所述，这些结果引起了关于咖啡因的骨骼生长毒性的重要关注，并可能表明成人骨质疏松症和骨关节炎的宫内起源。

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