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Developmental Toxicology

Genetic Toxicology, Oncogenesis, Developmental and Reproductive Toxicology

  1. John M. DeSesso PhD, DABFM, FATS1,2,
  2. Calvin C. Willhite PhD3

Published Online: 15 DEC 2009

DOI: 10.1002/9780470744307.gat084

General, Applied and Systems Toxicology

General, Applied and Systems Toxicology

How to Cite

DeSesso, J. M. and Willhite, C. C. 2009. Developmental Toxicology. General, Applied and Systems Toxicology. .

Author Information

  1. 1

    Exponent, Alexandria, Virginia, USA

  2. 2

    Georgetown University School of Medicine, NW, Washington DC, USA

  3. 3

    Department of Toxic Substance Control, State of California, Berkeley, California, USA

Publication History

  1. Published Online: 15 DEC 2009

Abstract

The full range of development that is subject to injury—be it a consequence of maternal disease, nutritional excess or deficiency, xenobiotic or radiation exposure or as a result of infectious agents - begins with the primordial germ cells of the individual's parents, proceeds through gametogenesis and concludes at the end of a person's natural life. The present chapter is focused upon understanding adverse reproductive outcome as a result of embryonic exposure to selected environmental chemicals and therapeutic drugs. The chapter begins with examples from ancient history and contemporary motion pictures, from the scientific literature and from the popular press. The text explains some of the fundamental steps taken and the genes involved in establishment of the vertebrate body plan. Examples are provided to illustrate how failure of proper gene expression and coordination at precise embryonic stages is responsible for the pathogenesis of specific congenital malformations. Consolidated presentations of experimental teratology and developmental toxicity studies are provided, along with the steps required to interpret the results of those studies in the context of human health risk assessment. The chapter contrasts the risks associated with misdirected speculation, irrational public fear and chemical rumors compared to the real public health consequences associated with maternal disease (e.g., alcoholism, diabetes, obesity) and nutritional deficiency (e.g., vitamin A, folates). The chapter concludes with the fundamental role of inappropriate embryonic gene expression in carcinogenesis. Increased understanding of genomic regulatory circuits in embryos has contributed to increased understanding of normal cell regeneration and turnover and how disturbances in those circuits lead to neoplasia and other degenerative diseases in children and adults.

Keywords:

  • birth defects;
  • risk of;
  • conjoined twins;
  • endocrine disruption;
  • foetal encephalopathy;
  • holoprosencephaly;
  • neurulation;
  • oral contraceptives;
  • primordial germ cells;
  • spina bifida;
  • teratogen;
  • teratology;
  • transforming growth factor (TGF)