What is Teratogensis
Introduction
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.[1]
Teratogens are substances that may cause birth defects via a toxic effect on an embryo
or fetus.[2] Known teratogens
include: thalidomide,[3] mercury,[4] alcohol,[5] lead,[6] and polychlorinated
biphenyls (PCBs).[7]
TeratogenesisEdit
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.[11] 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. One example of this is the use of
mammalian animal models to evaluate the molecular role of Teratogens in the
development of embryonic populations, such as the Neural Crest[12] , which can lead to
the development of Neurocristopathies. 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. Prenatal alcohol exposure (PAE) can produce
craniofacial malformations, a phenotype that is visible in Fetal Alcohol
Syndrome. [13] Current evidence suggests that craniofacial malformations occur via:
apoptosis of neural crest cells,[14] interference with neural crest cell migration, [15] [16] as
well as the disruption of sonic hedgehog (shh) signaling.[17]
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.
AlcoholEdit
Alcohol is known to act as a teratogen. [18] Prenatal alcohol exposure (PAE) remains
the leading cause of birth defects and neurodevelopmental abnormalities in the United
States, affecting 9.1 to 50 per 1000 live births in the U.S. and 68.0 to 89.2 per 1000 in
populations with high levels of alcohol abuse.[19]
HumansEdit
Main article: Congenital disorder
In humans, congenital disorders resulted in about 510,000 deaths globally in 2010.[20]
About 3% of newborns have a "major physical anomaly", meaning a physical anomaly
that has cosmetic or functional significance.[21]
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.[22] However, it is still not
recommended to vaccinate for polio while pregnant unless there is risk of
infection.[23] 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.[24]
CausesEdit
Further information: Congenital disorder
Causes of teratogenesis can broadly be classified as:
• Toxic substances, such as, for humans, drugs in pregnancy and environmental toxins in pregnancy.
o Potassium iodide is a possible teratogen. Potassium iodide in its raw form is a mild irritant and
should be handled with gloves. Chronic overexposure can have adverse effects on the thyroid.
• Vertically transmitted infection
• Lack of nutrients. For example, lack of folate acid in the nutrition in pregnancy for humans can
result in spina bifida. Folic acid is a synthetic form of folate acid. Folic is added to processed food
products, such as flour and breakfast cereals. High levels of un-metabolized folic acid have been
associated with several health problems.[25]
• Physical restraint. An example is Potter syndrome due to oligohydramnios in humans.
• Genetic disorders
• Alcohol consumption during pregnancy.
