Teratology

Teratology is the science dealing with the causes, mechanisms, and manifestations of developmental deviations of either structural or functional nature. It is an interdisciplinary field of embryology and pathology that focuses on abnormal development and congenital defects. Teratology is a basic medical science whose clinical counterpart is dysmorphology (branch of clinical genetics and pediatrics that also focuses on congenital defects).

Types

• Descriptive teratology
• Experimental teratology

Principles of Teratology

James G. Wilson (1959) proposed six principles of teratology that are still commonly used:^[1][2]

• Susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this interacts with environmental factors.
• Susceptibility to teratogens varies with the developmental stage at the time of exposure.
• Teratogenic agents act in specific ways on developing cells and tissues to initiate abnormal developmental processes.
• The final manifestations of abnormal development are death, malformation, growth retardation and functional disorder.
• The access of adverse environmental influences to developing tissues depends on the nature of the influence.
• Manifestations of deviant development increase in frequency and in degree as dosage increases from no effect to the 100% lethal (LD100) level.

Causes of Malformation

Structural congenital anomalies have stimulated numerous etiological studies. Some malformations have recognized genetic or teratogenic causes, but the majority have an unknown etiology (idiopathic conditions) or are caused by a combination of genetic and environmental factors, which are then considered risk factors that increase the liability of malformation.

• Genetic Disorders - Internal factors are believed to account for about 15%
  • Single-gene defects
  • Chromosomal aberrations
    • Aneuploidy (numerical abnormalities)
    • Structural abnormalities (deletions, insertions and rearrangements)
    • Chromosomal mosaicism
• Environmental Factors - External factors (teratogens) may account for about 10%
  • Chemicals, drugs, hormones, and vitamins
  • Infectious agents
  • Physical agents
  • Maternal conditions, including nutritional deficiencies and metabolic disorders
• Multifactorial and Idiopathic Disorders - Are presumed to account for about 75%

Critical Periods

Early spontaneous abortion

In the first 2 weeks after fertilization, this period of development is referred to as "predifferentiation," as this is before organ development has begun, and teratogen effects usually result in spontaneous abortion. Often the mother is not even aware of being pregnant during this time. Thus it is said that early embryos appear to be relatively insensitive to teratogens.

Critical or sensitive period

The critical period for sensitivity to structural teratogenesis, about the 3rd through the 8th post-fertilization week, is the period of embryogenesis, "early differentiation," or "early organogenesis," during which all the major organ systems of the body are being formed. Teratogen exposure during this time can result in significant structural anomalies (congenital malformations).

Organs and organ systems have overlapping sensitive periods. Teratogens have different effects, depending upon timing of exposure.

Fetal period and minor anomalies

The fetal period is characterized by growth and maturation of organs and tissues that formed during the embryonic period. A teratogen acting at this time is likely to have a less severe effect on fetal morphology but may result in minor structural anomalies or in functional disorders. However, even during the fetal period a few mechanisms, such as localized severe ischemia and amniotic bands, can cause significant disruptions or deformations of fetal anatomy.

Teratogens

A teratogen is an agent that can cause a defect or malformation in the development of the embryo or fetus. Several factors affect the ability of a teratogen to affect a developing conceptus. Such factors include the nature of the agent itself, the route, degree, timing, and duration of maternal exposure, the rate of placental transfer and systemic absorption, and the maternal and embryonic/fetal genotypes involved. Teratogens act in specific ways (e.g., cytotoxicity, mutation, chromosome damage, changing enzyme activity, altering patterns of apoptosis, etc.), often in specific tissues, so they typically produce characteristic congenital anomalies.

There are a few dozen proven human teratogens; however, many more factors are suspected based on case reports, retrospective studies, and animal experiments that have identified more than 600 potential teratogens. Human teratogens include the following types:

• Chemical agents:
  • Environmental pollutants: e.g., methylmercury, lead, and PCBs
  • Prescription and over-the-counter drugs: e.g., cancer chemotherapeutics and anticonvulsants
  • Recreational "drugs": e.g., ethanol
  • Hormones: e.g., androgenic steroids and DES
  • Vitamins: e.g., retinoids
• Infectious agents: e.g., toxoplasmosis, rubella, cytomegalovirus, herpes simplex and syphilis
• Physical agents: e.g., ionizing radiation and hyperthermia
• Maternal conditions: e.g., diabetes, malnutrition, obesity, and phenylketonuria

Developmental Defects

Developmental defects include embryonic and fetal death, intrauterine growth retardation, and structural and functional congenital anomalies. Major anomalies are those that affect survival, function or social acceptability. Minor anomalies have little or no medical or cosmetic consequence.

• Prenatal Death (miscarriage and stillbirth)
• Intrauterine Growth Retardation
• Congenital Anomalies (Birth Defects)
  • Structural Defects
    • Macroscopic structural defects
      • Malformations
      • Disruptions
      • Deformations
    • Microscopic structural defects (dysplasias)
  • Functional Defects
    • Inborn errors of metabolism
    • Physiological disturbances
    • Mental retardation
    • Cellular and molecular abnormalities

History

Étienne Geoffroy Saint-Hilaire (1772-1844) has been called the founder of teratology.^[3] He wrote of various malformations, e.g., anencephaly, spina bifida, and conjoined twins, in humans, including Egyptian mummies. He induced malformations in chick embryos and suggested that they were caused by arrests or delays in development.
John William Ballantyne (1861-1923), a Scottish obstetrician who wrote an influential two-volume book on the pathology of diseases of embryos and fetuses, was a pioneering advocate of antenatal care to prevent congenital anomalies.^[4]

How Teratology Was Named

The English word teratology is derived from the Greek word τερατολογία (teratologia, "a telling of marvels"), which has the roots τερας (teras, "marvel" or 'monster") and λόγος (logos, "word" or "treatise"). It appears in English dictionaries as early as the 17th century with the same meaning as the original Greek word. In the 19th century, Isidore Geoffroy Saint Hilaire (1805-1861), the son of Étienne, may have reinvented the word teratologie when he used it to mean the study of congenital malformations^[5]. This new meaning appeared in English medical dictionaries in about a decade.

References

1. ↑ Wilson JG. Experimental studies on congenital malformations. J Chron Dis 10:111-130, 1959.
2. ↑ Wilson JG. Environment and Birth Defects. New York: Academic Press, 1973.
3. ↑ Geoffroy Saint-Hilaire E. Philosophie anatomique: Des monstruosités humaines. Paris: J.B. Baillière, 1822.
4. ↑ Ballantyne JW. Manual of Antenatal Pathology and Hygiene. 2 vols. Edinburgh: William Green & Sons, 1902-04.
5. ↑ Geoffroy Saint Hilaire I. Histoire générale et particulière des anomalies de l’organisation chez l’homme et les animaux. Paris: J.-B. Baillière, 1832-37.

External Links

Teratology Society
Organization of Teratology Information Specialists
Clinical Teratology Web - TERIS (Teratogen Information System) at University of Washington