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香烟烟雾通过下调 noggin 表达诱导神经管缺陷。

Cigarette smoke induced neural tube defects by down-regulating noggin expression.

机构信息

Department of Histology and Embryology, Binzhou Medical University, Yantai, Shandong, China.

Department of introduction to medicine, School of basic medicine, Shandong first medical university & Shandong academy of medical sciences, Shandong, China.

出版信息

Birth Defects Res. 2021 Jan 1;113(1):5-13. doi: 10.1002/bdr2.1804. Epub 2020 Sep 19.

Abstract

BACKGROUND

Maternal smoking or passive smoking during gestation increases the risk of congenital birth defects, including neural tube defects (NTDs). Cigarette smoke is a recognized teratogen that causes NTDs, although the mechanisms are not well understood.

METHODS

An established model of passive smoking in pregnant golden hamsters was used to observe the effect of cigarette smoke on neural tube development using scanning electron microscopy. Level of noggin expression in placenta and neural tube was evaluated by immunohistochemistry.

RESULTS

Our results indicated that cigarette smoke can cause the neural tube closure of the golden hamster embryo to be delayed or not closed. In normal placental tissues noggin protein and RNA levels were highly expressed, and the expression level in the term placenta was lower than in that of the first trimester or second trimester through analyzing the Human Protein Atlas and the Gene Expression Omnibus (GEO) databases. Cigarette smoke can down-regulate noggin expression in the placenta and promote cell apoptosis. We observed that noggin expression was reduced and BMP2 expression was increased by cigarette smoke.

CONCLUSIONS

Cigarette smoke may cause cell apoptosis and accelerate placenta maturation. Meanwhile, cigarette smoke may inhibit the development of the embryo, and lead to the formation of NTDs via downregulating the expression of noggin and dis-inhibition of BMP2.

摘要

背景

母体在妊娠期间吸烟或被动吸烟会增加先天性出生缺陷的风险,包括神经管缺陷(NTDs)。香烟烟雾是一种公认的致畸物,会导致 NTDs,但具体机制尚不清楚。

方法

我们使用已建立的孕期金黄地鼠被动吸烟模型,通过扫描电子显微镜观察香烟烟雾对神经管发育的影响。通过免疫组织化学评估胎盘和神经管中 noggin 表达水平。

结果

我们的结果表明,香烟烟雾会导致金黄地鼠胚胎的神经管闭合延迟或未闭合。在正常胎盘组织中,noggin 蛋白和 RNA 水平高度表达,通过分析人类蛋白质图谱(Human Protein Atlas)和基因表达综合数据库(GEO),我们发现胎盘组织中 noggin 的表达水平在足月时低于早孕期或中孕期。香烟烟雾可以下调胎盘组织中的 noggin 表达并促进细胞凋亡。我们观察到香烟烟雾使 noggin 表达减少,BMP2 表达增加。

结论

香烟烟雾可能通过诱导细胞凋亡和加速胎盘成熟来影响胚胎发育,导致 NTDs 的形成。此外,香烟烟雾可能通过下调 noggin 的表达和抑制 BMP2 的作用来抑制胚胎发育。

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