产前泼尼松暴露影响胎鼠肝脏发育和功能及其特征

IF 3.4 3区 医学 Q2 TOXICOLOGY
Yongguo Dai, Yu Peng, Zhengjie Lu, Tongyun Mao, Kaiqi Chen, Xiaoqian Lu, Kexin Liu, Xinli Zhou, Wen Hu, Hui Wang
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引用次数: 0

摘要

泼尼松(Prednisone)是一种广泛应用于人类和兽医的糖皮质激素药物,有报道称它会导致发育毒性。然而,有关泼尼松对胎儿肝脏发育影响的系统研究仍不清楚。我们研究了母体在不同妊娠期暴露于临床等效剂量的泼尼松对胎鼠肝脏细胞增殖和凋亡、细胞分化、糖和脂代谢以及造血的潜在影响,并探讨了其潜在机制。结果表明,产前泼尼松暴露(PPE)可抑制胎鼠肝脏的细胞增殖,抑制肝细胞分化,促进胆管细胞分化。同时,PPE 还能促进胎儿肝脏中的糖元生成和胆汁酸合成,抑制脂肪酸 β 氧化和造血。进一步分析发现,PPE 诱导的肝脏发育改变具有明显的阶段性和性别差异。总体而言,PPE 对胎儿肝脏发育和功能的改变在整个孕期(GD0-10)最为明显,男性受影响程度相对高于女性。此外,PPE 还抑制了胎儿肝脏的胰岛素样生长因子 1(IGF1)信号通路。总之,PPE 会影响胎儿肝脏的发育和多种功能,而这些改变可能与 IGF1 信号通路受到抑制有部分关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prenatal prednisone exposure impacts liver development and function in fetal mice and its characteristics.

Prednisone, a widely used glucocorticoid drug in human and veterinary medicine, has been reported to cause developmental toxicity. However, systematic studies about the effect of prednisone on fetal liver development are still unclear. We investigated the potential effects of maternal exposure to clinically equivalent doses of prednisone during different gestational stages on cell proliferation and apoptosis, cell differentiation, glucose and lipid metabolism, and hematopoiesis in the liver of fetal mice, and explored the potential mechanisms. Results showed that prenatal prednisone exposure (PPE) could suppress cell proliferation, inhibit hepatocyte differentiation, and promote cholangiocyte differentiation in the fetal liver. Meanwhile, PPE could result in the enhancement of glyconeogenesis and bile acid synthesis and the inhibition of fatty acid β-oxidation and hematopoiesis in the fetal liver. Further analysis found that PPE-induced alterations in liver development had obvious stage and sex differences. Overall, the alteration in fetal liver development and function induced by PPE was most pronounced during the whole pregnancy (GD0-18), and the males were relatively more affected than the females. Additionally, fetal hepatic insulin-like growth factor 1 (IGF1) signaling pathway was inhibited by PPE. In conclusion, PPE could impact fetal liver development and multiple functions, and these alterations might be partially related to the inhibition of IGF1 signaling pathway.

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来源期刊
Toxicological Sciences
Toxicological Sciences 医学-毒理学
CiteScore
7.70
自引率
7.90%
发文量
118
审稿时长
1.5 months
期刊介绍: The mission of Toxicological Sciences, the official journal of the Society of Toxicology, is to publish a broad spectrum of impactful research in the field of toxicology. The primary focus of Toxicological Sciences is on original research articles. The journal also provides expert insight via contemporary and systematic reviews, as well as forum articles and editorial content that addresses important topics in the field. The scope of Toxicological Sciences is focused on a broad spectrum of impactful toxicological research that will advance the multidisciplinary field of toxicology ranging from basic research to model development and application, and decision making. Submissions will include diverse technologies and approaches including, but not limited to: bioinformatics and computational biology, biochemistry, exposure science, histopathology, mass spectrometry, molecular biology, population-based sciences, tissue and cell-based systems, and whole-animal studies. Integrative approaches that combine realistic exposure scenarios with impactful analyses that move the field forward are encouraged.
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