Teratology

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A two-headed calf.

Teratology is the study of abnormalities of physiological development.
It is often thought of as the study of birth defects, but it is
much broader than that, taking in other developmental stages, such as puberty; and other life forms,
such as plants.

Contents

1 Etymology

2 In humans and other
mammals

2.1 Teratogenesis

2.1.1 Wilson's 6
principles

2.2 Teratology
education

2.3 Teratogenic
agents

2.4 Teratogenic
outcomes

3 In plants

4 See also

5 References

6 External
links

[edit]
Etymology

The term stems from the Greek τέρᾰς (téras, genitive τέρᾰτος- tératos), meaning monster, or
marvel and λόγος - lógos, meaning
speech or, more loosely, the study of.

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.[1]
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.

[edit]
In humans and other
mammals

[edit]
Teratogenesis

Birth defects are known to occur in 3-5% of all newborns.[2]
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.[3]
And although significant progress has been made in identifying the etiology of
some birth defects, approximately 65% have no known or identifiable cause.[4]

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.[5]

[edit]
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.[6]
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.

[edit]
Teratology education

It is estimated that 10% of all birth defects are caused by prenatal exposure
to a teratogenic agent.[4]
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.[7]
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.[8]

[edit]
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:

Drugs and medications: tobacco, caffeine, drinking alcohol (ethanol) (see fetal
alcohol spectrum disorder), isotretinoin
(13-cis-retinoic acid, Roaccutane), temazepam (Restoril;
Normisson), nitrazepam
(Mogadon), nimetazepam
(Ermin), aminopterin or
methotrexate, androgenic hormones, busulfan, captopril, enalapril, coumarin, cyclophosphamide, diethylstilbestrol,
phenytoin
(diphenylhydantoin, Dilantin, Epanutin), etretinate, lithium, methimazole, penicillamine, tetracyclines, thalidomide, trimethadione,
methoxyethyl ethers, Flusilazole, valproic acid, and many
more.

Environmental chemicals: polychlorinated
biphenyls (PCBs), polychlorinated
dibenzodioxins a.k.a dioxin, polychlorinated
dibenzofurans (PCDFs), hexachlorobenzene hexachlorophene, organic mercury, ethidium bromide,
etc.

Ionizing radiation: atomic weapons fallout
(Iodine-131, uranium), background
radiation, diagnostic x-rays, radiation
therapy

Infections: cytomegalovirus, herpes virus, parvovirus B19, rubella virus
(German measles), syphilis, toxoplasmosis, Venezuelan
equine encephalitis virus. (An easy way to remember maternal infections is
TORCH: Toxoplasmosis, Other agents, Rubella, CMV and HSV.

Metabolic imbalance: alcoholism, endemic
cretinism, diabetes, folic acid
deficiency, iodine deficiency,
hyperthermia, phenylketonuria, rheumatic disease
and congenital heart block, virilizing
tumors

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,[9]
nicotine,[10]
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.[11][12]

[edit]
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.

[edit]
In plants

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.

[edit]
See also

Biology
portal

Carcinogen

Congenital
abnormalities

Mutagen

[edit]
References

^
Jones, K.L., Smith, D.W, Ulleland, C.N., Streissguth, A.P. (1973). Pattern of
malformation in offspring of chronic alcoholic mothers. Lancet,
1, 1267–1271. PMID 4126070

^ "Birth
Defects & Genetics: Birth Defects". http://www.marchofdimes.com/pnhec/4439_1206.asp. Retrieved 2007-05-30.

^
Dicke JM (1989). "Teratology: principles and
practice". Med. Clin. North Am. 73 (3): 567–82. PMID 2468064.

^ a
b
Ronan O'Rahilly, Fabiola Müller (2001). Human
embryology & teratology. New York: Wiley-Liss. ISBN 0-471-38225-6.

^ van Gelder MM, van Rooij IA, Miller RK, Zielhuis GA,
de Jong-van den Berg LT, Roeleveld N (January 2010). "Teratogenic mechanisms
of medical drugs". Hum Reprod Update 16 (4): 378–94. doi:10.1093/humupd/dmp052. PMID 20061329.

^
James G. Wilson, (1973). Environment and Birth
Defects (Environmental Science Series). London: Academic Pr. ISBN 0-12-757750-5.

^
Bracken MB, Holford TR (1981). "Exposure to
prescribed drugs in pregnancy and association with congenital malformations".
Obstetrics and gynecology 58 (3): 336–44. PMID 7266953.

^
King CR (1986). "Genetic counseling for
teratogen exposure". Obstetrics and gynecology 67 (6): 843–6. doi:10.1097/00006250-198606000-00020. PMID 3703408.

^
Linnainmaa K (1983). "Sister chromatid
exchanges among workers occupationally exposed to phenoxy acid herbicides
2,4-D and MCPA". Teratog., Carcinog. Mutagen. 3 (3): 269–79. doi:10.1002/1520-6866(1990)3:3<269::AID-TCM1770030306>3.0.CO;2-F.
PMID 6137083.

^
Vaglenova J, Birru S, Pandiella NM, Breese CR
(2004). "An assessment of the long-term developmental and behavioral
teratogenicity of prenatal nicotine exposure". Behav. Brain Res.
150 (1-2): 159–70. doi:10.1016/j.bbr.2003.07.005. PMID 15033289.

^
Hunt JR (1996). "Teratogenicity of high vitamin
A intake". N. Engl. J. Med. 334 (18): 1197. doi:10.1056/NEJM199605023341814. PMID 8602195.

^
Hartmann S, Brørs O, Bock J, et al.
(2005). "Exposure to retinoic acids in non-pregnant women following high
vitamin A intake with a liver meal". International journal for vitamin and
nutrition research. Internationale Zeitschrift für Vitamin- und
Ernährungsforschung. Journal international de vitaminologie et de
nutrition 75 (3): 187–94. PMID 16028634.

[edit]
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)

List of known and suspected Teratogens (Hazard
Database)

Retrieved from "http://en.wikipedia.org/wiki/Teratology"

Categories: Developmental
biology | Radiation
health effects | Teratogens

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