Abnormal Development - Thalidomide

Introduction

How and why do things go wrong in development?

Some Recent Findings

Identification of a primary target of thalidomide teratogenicity^[1] "Here, we identified cereblon (CRBN) as a thalidomide-binding protein. CRBN forms an E3 ubiquitin ligase complex with damaged DNA binding protein 1 (DDB1) and Cul4A that is important for limb outgrowth and expression of the fibroblast growth factor Fgf8 in zebrafish and chicks. Thalidomide initiates its teratogenic effects by binding to CRBN and inhibiting the associated ubiquitin ligase activity. This study reveals a basis for thalidomide teratogenicity and may contribute to the development of new thalidomide derivatives without teratogenic activity."

Cereblon

Cereblon was named based on its putative role in cerebral development and the highly conserved Lon domain. Functionally it had been previously identified as being associated with neural development.

Links: OMIM - Cereblon

Teratology

Now consider how different environmental effects during pregnancy may influence developmental outcomes. The terms listed below are often used to describe these environmental effects

Teratogen (Greek, teraton = monster) any agent that causes a structural abnormality (congenital abnormalities) following fetal exposure during pregnancy. The overall effect depends on dosage and time of exposure. (More? Critical Periods of Development)

Absolute risk the rate of occurrence of an abnormal phenotype among individuals exposed to the agent. (e.g. fetal alcohol syndrome)

Relative risk the ratio of the rate of the condition among the exposed and the nonexposed. (e.g. smokers risk of having a low birth weight baby compared to non-smokers) A high relative risk may indicate a low absolute risk if the condition is rare.

Mutagen a chemical or agent that can cause permanent damage to the deoxyribonucleic acid (DNA) in a cell. DNA damage in the human egg or sperm may lead to reduced fertility, spontaneous abortion (miscarriage), birth defects and heritable diseases.

Fetotoxicant is a chemical that adversely affects the developing fetus, resulting in low birth weight, symptoms of poisoning at birth or stillbirth (fetus dies before it is born).

Synergism when the combined effect of exposure to more than one chemical at one time, or to a chemical in combination with other hazards (heat, radiation, infection) results in effects of such exposure to be greater than the sum of the individual effects of each hazard by itself.

Toxicogenomics the interaction between the genome, chemicals in the environment, and disease. Cells exposed to a stress, drug or toxicant respond by altering the pattern of expression of genes within their chromosomes. Based on new genetic and microarray technologies.

References

↑ <pubmed>20223979 </pubmed>

Reviews

Articles

Search Pubmed

June 2010 "thalidomide teratogenicity" All (147) Review (57) Free Full Text (11)

Search Pubmed: thalidomide teratogenicity | Thalidomide

UNSW Embryology Links

Abnormal Development
Abnormal Development- Australian Statistics | Abnormalities by Systems
Prenatal Diagnosis
Genetic Abnormalities | Down Syndrome | Edwards Syndrome | Fragile X | Lesch-Nyhan Syndrome
Maternal Factors | Maternal Diabetes | Maternal Hyperthermia | Neural Tube Defects | Fetal Alcohol Syndrome | Smoking | Chemical | Drugs | Illegal Drugs | Radiation | Heavy Metal | Iodine Deficiency | Viral Infection | Rubella | Polio | Parvovirus | Varicella | Bacterial Infection | Malaria | Toxoplasmosis | Autism
Fetal Origins Hypothesis
Intrauterine Growth Retardation
Twinning

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Cite this page: Hill, M.A. (2024, May 4) Embryology Abnormal Development - Thalidomide. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Thalidomide

What Links Here?

[PMID20223979-1] <pubmed>20223979 </pubmed>

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