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

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.

Keywords: Birth defects; Congenital malformations; Critical period; Developmental pharmacology; Developmental toxicology; Fetal examination; Freehand razor sectioning technique; Laboratory animal; Rodent; Skeletal staining technique; Teratogen; Teratology.

MeSH terms

  • Abnormalities, Drug-Induced / diagnosis*
  • Abnormalities, Drug-Induced / genetics
  • Animals
  • Bone and Bones / abnormalities
  • Bone and Bones / drug effects
  • Bone and Bones / embryology
  • Congenital Abnormalities / diagnosis*
  • Congenital Abnormalities / genetics
  • Female
  • Fetus / abnormalities
  • Fetus / drug effects
  • Humans
  • Mice
  • Pregnancy
  • Rats
  • Teratogens / toxicity*

Substances

  • Teratogens