Teratology(Redirected from Teratogen)
Teratology is the study of abnormalities of physiological development. It is often thought of as the study of human congenital abnormalities, but it is broader than that, taking into account other non-birth developmental stages, including puberty; and other organisms, including plants. The related term developmental toxicity includes all manifestations of abnormal development that are caused by environmental insult. These may include growth retardation, delayed mental development or other congenital disorders without any structural malformations.
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. Historically, people have used many pejorative terms to describe/label cases of significant physical malformations. In the 1960s 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), popularized the term teratology. With the growth of understanding of the origins of birth defects, the field of teratology as of 2015[update] overlaps with other fields of science, including developmental biology, embryology, and genetics. Until the 1940s teratologists regarded birth defects as primarily hereditary. In 1941 the first well-documented cases of environmental agents being the cause of severe birth defects were reported[by whom?].
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. These principles guide the study and understanding of teratogenic agents and their effects on developing organisms:
- Susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this interacts with adverse environmental factors.
- 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.
- Teratogenic agents act in specific ways on developing cells and tissues to initiate sequences of abnormal developmental events.
- 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.
- There are four manifestations of deviant development (Death, Malformation, Growth Retardation and Functional Defect).
- 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.
About 3% of newborns have a "major physical anomaly", meaning a physical anomaly that has cosmetic or functional significance.
Vaccinating while pregnantEdit
In humans, vaccination has become readily available, and is important to the prevention of some diseases like polio, rubella, and smallpox, among others. There has been no association between congenital malformations and vaccination, as shown in Finland in which expecting mothers received the oral polio vaccine and saw no difference in infant outcomes than mothers who had not received the vaccine. However, it is still not recommended to vaccinate for polio while pregnant due to possible complications for the mother. Another important implication of this includes the ability to get the influenza vaccine while pregnant. During the 1918 and 1957 influenza pandemics, mortality in pregnant women was 45%. However, even with prevention through vaccination, influenza vaccination in pregnant women remains low at 12%. Munoz et al. demonstrated that there was no adverse outcomes observed in the new infants or mothers.
Causes of teratogenesis can broadly be classified as:
- Toxic substances, such as, for humans, drugs in pregnancy and environmental toxins in pregnancy.
- Vertically transmitted infection
- Lack of nutrients. For example, lack of folic acid in the nutrition in pregnancy for humans can result in spina bifida.
- Physical restraint. An example is Potter syndrome due to oligohydramnios in humans.
- Genetic disorders
- Alcohol consumption during pregnancy.
Evidence for congenital deformities found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury. Fossils bearing evidence of congenital deformity are scientifically significant because they can help scientists infer the evolutionary history of life's developmental processes. For instance, because a Tyrannosaurus rex specimen has been discovered with a block vertebra, it means that vertebrae have been developing the same basic way since at least the most recent common ancestor of dinosaurs and mammals. Other notable fossil deformities include a hatchling specimen of the bird-like dinosaur, Troodon, the tip of whose jaw was twisted. Another notably deformed fossil was a specimen of the choristodere Hyphalosaurus, which had two heads- the oldest known example of polycephaly.
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.
- Rogers, J.M., Kavlock, R.J. (1996). "Developmental toxicology". In C.D. Klaassen (ed.): Casarett & Doull's Toxicology, (5th ed.). pp. 301-331. New York: McGraw-Hill. ISBN 0-07-105476-6.
- Thall Bastow BD, Holmes JL (23 February 2016). "Teratology and drug use during pregnancy". Medscape. WebMD. Retrieved 24 February 2016.
- "Online Etymology Dictionary". Etymologyonline.com. Retrieved 8 April 2011.
- Jones K.L.; Smith D.W; Ulleland C.N.; Streissguth A.P. (1973). "Pattern of malformation in offspring of chronic alcoholic mothers". Lancet. 1 (7815): 1267–1271. doi:10.1016/S0140-6736(73)91291-9. PMID 4126070.
- "Birth Defects". Howmed.net. Retrieved 2015-11-01.
Until 1940, it was assumed that congenital defects were caused primarily by hereditary factors. In 1941, the first well-documented cases were reported that an environmental agent (rubella virus) could produce severe anatomic anomalies.
- James G. Wilson (1973). Environment and Birth Defects (Environmental Science Series). London: Academic Pr. ISBN 0-12-757750-5.
- Lozano, R (December 2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. PMID 23245604.
- Kumar, Abbas and Fausto (eds.), Robbins and Cotran's Pathologic Basis of Disease, 7th edition, p. 470.
- Harjulehto-Mervaala, T (1993). "Oral Polio Vaccination during Pregnancy: No Increase in the Occurrence of Congenital Malformations". American Journal of Epidemiology. 138 (6): 407–414. PMID 8213746.
- Munoz, F (2005). "Safety of influenza vaccination during pregnancy". American Journal of Obstetrics and Gynecology. 192: 1098–1106. doi:10.1016/j.ajog.2004.12.019.
- Molnar, R. E., 2001, Theropod paleopathology: a literature survey: In: Mesozoic Vertebrate Life, edited by Tanke, D. H., and Carpenter, K., Indiana University Press, p. 337-363.
- Ji Q.; Wu X.-C.; Cheng Y.-N. (2010). "Cretaceous choristoderan reptiles gave birth to live young". Naturwissenschaften. 97 (4): 423–428. doi:10.1007/s00114-010-0654-2. PMID 20179895.