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胎儿大体畸形评估:现代化的威尔逊技术与骨骼染色

Assessment of Gross Fetal Malformations: The Modernized Wilson Technique and Skeletal Staining.

作者信息

Seegmiller Robert E, Cook Nathan, Goodwin Korance, Leishman Timothy, Graf Michelle

机构信息

Department of Physiology and Developmental Biology, College of Life Sciences, Brigham Young University, Provo, UT, USA.

出版信息

Methods Mol Biol. 2019;1965:421-434. doi: 10.1007/978-1-4939-9182-2_27.

Abstract

Teratology is the study of anatomical and physiological abnormalities, commonly known as birth defects. If an embryo is exposed to a harmful substance, or teratogen, during the critical period of development, an ensuing malformation may occur. These malformations and their associated mechanisms are studied and analyzed in laboratory animals in order to prevent them from occurring in humans. Rodents such as rats and mice have commonly been used in such studies because of their similarity to humans. In 1959, James G. Wilson designed, developed, and tested a protocol on how to observe and analyze structural malformations in rodent fetuses, which included: external examination, skeletal evaluation, soft tissue analysis, and data collection/analysis. For standardization purposes, i.e., to normalize findings from one lab to another, it is important that this protocol be followed with precision. Although many years have passed since Wilson initially created this protocol, it is still widely used to this day, and only minor changes have been made to his instructions such as the chemical reagents used in the experiments and methods of analysis of the experimental data. Such testing has resulted in major advances in the dissemination of teratology information, including the identification of an increasing number of teratogens and the understanding of the pathogenesis of birth defects. While mechanistically birth defect prevention will include the understanding of individual genomes and pharmacogenomics, overall, morphological assessment will still be required as an integral part of birth defects research. As the interaction between teratogenic and genetic factors is better understood, it is anticipated that the incidence of most types of defects will substantially be reduced.

摘要

畸形学是对解剖学和生理学异常(通常称为出生缺陷)的研究。如果胚胎在发育的关键时期接触到有害物质或致畸剂,随后可能会出现畸形。为了防止这些畸形在人类中发生,人们在实验动物中对这些畸形及其相关机制进行研究和分析。由于大鼠和小鼠等啮齿动物与人类相似,它们通常被用于此类研究。1959年,詹姆斯·G·威尔逊设计、开发并测试了一个关于如何观察和分析啮齿动物胎儿结构畸形的方案,该方案包括:外部检查、骨骼评估、软组织分析以及数据收集/分析。为了实现标准化,即把一个实验室的研究结果标准化到另一个实验室,精确遵循这个方案很重要。尽管自威尔逊最初创建这个方案以来已经过去了很多年,但它至今仍被广泛使用,并且他的指导说明只做了一些小的改动,比如实验中使用的化学试剂以及实验数据分析方法。这样的测试在畸形学信息传播方面取得了重大进展,包括识别出越来越多的致畸剂以及对出生缺陷发病机制的理解。虽然从机制上讲,出生缺陷的预防将包括对个体基因组和药物基因组学的理解,但总体而言,形态学评估仍将作为出生缺陷研究的一个组成部分而被需要。随着致畸因素和遗传因素之间的相互作用被更好地理解,预计大多数类型缺陷的发生率将大幅降低。

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