World Library  
Flag as Inappropriate
Email this Article

Teratogen

Article Id: WHEBN0000249308
Reproduction Date:

Title: Teratogen  
Author: World Heritage Encyclopedia
Language: English
Subject: Zebrafish, Carcinogen, Testosterone, Toxicity, Index of genetics articles, Index of genetic engineering articles, Causes of autism, Outline of nutrition
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Teratogen

Teratology is the study of abnormalities of physiological development. It is often thought of as the study of human birth defects, but it is much broader than that, taking in other non-birth developmental stages, including puberty; and other non-human life forms, including plants. A newer term developmental toxicity includes all manifestations of abnormal development. These may include growth retardation or delayed mental development without any structural malformations.[1]

Etymology

The term stems from the Greek τέρας teras (genitive τέρατος teratos), meaning 'monster' or 'marvel', and λόγος logos, meaning 'the word' or, more loosely, 'the study of'.[2]

As early as the 17th century, teratology referred to a discourse on prodigies and marvels of anything so extraordinary as to seem abnormal. In the 19th century, it acquired a meaning more closely related to biological deformities, mostly in the field of botany. Currently, its most instrumental meaning is that of the medical study of teratogenesis, congenital malformations or individuals with significant malformations. There are many pejorative terms that have historically been used to describe individuals with significant physical malformations. The term was popularized in the 1960s by Dr. David W. Smith of the University of Washington Medical School, one of the researchers who became known in 1973 for the discovery of Fetal alcohol syndrome.[3] With greater understanding of the origins of birth defects, the field of teratology now overlaps with other fields of basic science, including developmental biology, embryology, and genetics.

Animalia

Teratogenesis

Birth defects are known to occur in 3-5% of all newborns.[4] They are the leading cause of infant mortality in the United States, accounting for more than 20% of all infant deaths. Seven to ten percent of all children will require extensive medical care to diagnose or treat a birth defect.[5] And although significant progress has been made in identifying the etiology of some birth defects, approximately 65% have no known or identifiable cause.[6]

It was previously believed that the mammalian embryo developed in the impervious uterus of the mother, protected from all extrinsic factors. However, after the thalidomide disaster of the 1960s, it became apparent and more accepted that the developing embryo could be highly vulnerable to certain environmental agents that have negligible or non-toxic effects to adult individuals.

A review published in 2010 identified 6 main teratogenic mechanisms associated with medication use: folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress, vascular disruption and specific receptor- or enzyme-mediated teratogenesis.[7]

Wilson's 6 principles

Along with this new awareness of the in utero vulnerability of the developing mammalian embryo came the development and refinement of The Six Principles of Teratology which are still applied today. These principles of teratology were put forth by Jim Wilson in 1959 and in his monograph Environment and Birth Defects.[8] These principles guide the study and understanding of teratogenic agents and their effects on developing organisms:

  1. Susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this interacts with adverse environmental factors.
  2. Susceptibility to teratogenesis varies with the developmental stage at the time of exposure to an adverse influence. There are critical periods of susceptibility to agents and organ systems affected by these agents.
  3. Teratogenic agents act in specific ways on developing cells and tissues to initiate sequences of abnormal developmental events.
  4. The access of adverse influences to developing tissues depends on the nature of the influence. Several factors affect the ability of a teratogen to contact a developing conceptus, such as the nature of the agent itself, route and degree of maternal exposure, rate of placental transfer and systemic absorption, and composition of the maternal and embryonic/fetal genotypes.
  5. There are four manifestations of deviant development (Death, Malformation, Growth Retardation and Functional Defect).
  6. Manifestations of deviant development increase in frequency and degree as dosage increases from the No Observable Adverse Effect Level (NOAEL) to a dose producing 100% Lethality (LD100).

Studies designed to test the teratogenic potential of environmental agents use animal model systems (e.g., rat, mouse, rabbit, dog, and monkey). Early teratologists exposed pregnant animals to environmental agents and observed the fetuses for gross visceral and skeletal abnormalities. While this is still part of the teratological evaluation procedures today, the field of Teratology is moving to a more molecular level, seeking the mechanism(s) of action by which these agents act. Genetically modified mice are commonly used for this purpose. In addition, pregnancy registries are large, prospective studies that monitor exposures women receive during their pregnancies and record the outcome of their births. These studies provide information about possible risks of medications or other exposures in human pregnancies.

Understanding how a teratogen causes its effect is not only important in preventing congenital abnormalities but also has the potential for developing new therapeutic drugs safe for use with pregnant women.

Teratology education

It is estimated that 10% of all birth defects are caused by prenatal exposure to a teratogenic agent.[6] These exposures include, but are not limited to, medication or drug exposures, maternal infections and diseases, and environmental and occupational exposures. Teratogen-caused birth defects are potentially preventable. Studies have shown that nearly 50% of pregnant women have been exposed to at least one medication during gestation.[9] An additional study found that of 200 individuals referred for genetic counseling for a teratogenic exposure, 52% were exposed to more than one potential teratogen.[10]

Teratogenic agents

A wide range of different chemicals and environmental factors are suspected or are known to be teratogenic in humans and in animals. A selected few include:

The status of some of the above substances (e.g. diphenylhydantoin) is subject to debate, and many other compounds are under varying degrees of suspicion. These include Agent Orange,[11] nicotine,[12] aspirin and other NSAIDs. Other compounds are known as severe teratogens based on veterinary work and animal studies, but aren't listed above because they have not been studied in humans, e.g. cyclopamine. Teratogenic effects also help to determine the pregnancy category assigned by regulatory authorities; in the United States, a pregnancy category of X, D, or C may be assigned if teratogenic effects (or other risks in pregnancy) are documented or cannot be excluded.

Isotretinoin (13-cis-retinoic-acid; brand name Roaccutane), which is often used to treat severe acne, is such a strong teratogen that just a single dose taken by a pregnant woman may result in serious birth defects. Because of this effect, most countries have systems in place to ensure that it is not given to pregnant women, and that the patient is aware of how important it is to prevent pregnancy during and at least one month after treatment. Medical guidelines also suggest that pregnant women should limit vitamin A intake to about 700 μg/day, as it has teratogenic potential when consumed in excess.[13][14]

Teratogenic outcomes

Exposure to teratogens can result in a wide range of structural abnormalities such as cleft lip, cleft palate, dysmelia, anencephaly, ventricular septal defect. Exposure to a single agent can produce various abnormalities depending on the stage of development it occurs. Specific birth defects are not characteristic of any single agent.

Plantae

In botany, teratology investigates the theoretical implications of abnormal specimens. For example, the discovery of abnormal flowers—for example, flowers with leaves instead of petals, or flowers with staminoid pistils—furnished important evidence for the "foliar theory", the theory that all flower parts are highly specialised leaves.

Nuclear weapon survivors

The survivors of the atomic bombing of Hiroshima and Nagasaki, who are known as the Hibakusha, were (and still are) victims of severe discrimination due to public ignorance about the consequences of radiation sickness, with much of the public believing it to be hereditary or even contagious.[15] This is despite the fact that no statistically demonstrable increase of birth defects/congenital malformations was found among the later conceived children born to survivors of the nuclear weapons used at Hiroshima and Nagasaki, or found in the later conceived children of cancer survivors who had previously received radiotherapy.[16][17][18][19] The surviving women of Hiroshima and Nagasaki who were able to conceive, though exposed to substantial amounts of radiation, went on and had children with no higher incidence of abnormalities/birth defects than in the Japanese population as a whole.[20][21]

See also

Biology portal

References

External links

  • Society of Teratology
  • European Teratology Society
  • Organization of Teratology Information Specialists
  • March of Dimes Foundation
  • A Telling of Wonders: Teratology in Western Medicine through 1800 (New York Academy of Medicine Historical Collections)
  • The Reproductive Toxicology Center Database

de:Teratologie

et:Teratoloogia fr:Tératologie he:טרטולוגיה pl:Teratologia sl:Teratologija sv:Teratologi

This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.