Abnormal Development - Teratogens

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Human critical periods of development

How and why do things go wrong in development? Embryological development is a robust biological system able to cope with many stresses without long-term consequences. When development does go wrong there are generally 3 major types groups: Genetic (inherited), Environmental (maternal) derived and Unknown (not determined or known) abnormalities. Also often not considered, is that pregnancy itself can also expose abnormalities in the mother (congenital heart disease, diabetes, reproductive disorders) that until the pregnancy had gone undetected.

  • Infections collectively grouped under the acronym TORCH for Toxoplasmosis, Other organisms (parvovirus, HIV, Epstein-Barr, herpes 6 and 8, varicella, syphilis, enterovirus) , Rubella, Cytomegalovirus and Hepatitis. See also the related topics on maternal hyperthermia and bacterial infections.
  • Maternal diet the best characterised is the role of low folic acid and Neural Tube Defects (NTDs) see also abnormal neural development and Neural Tube Defects (NTDs). More recently the focus has been on dietary iodine levels and the role they also play on neural development.
  • Maternal drugs effects either prescription drugs (therapeutic chemicals/agents, thalidomide limb development), non-prescription drugs (smoking), and illegal drugs (Cannabis/Marijuana, Methamphetamine/Amphetamine, Cocaine, Heroin, Lysergic Acid Diethylamide). Some therapeutic compounds have teratogenic effects because they are also naturally occurring developmental signals, for example retinoic acid.
  • Environment (smoking, chemicals, heavy metals, radiation) and maternal endocrine function (maternal diabetes, thyroid development) and maternal stress.
  • Teratogen synergism, different environmental effects can act individually or in combination on the same developing system. For example, neural development can be impacted upon by alcohol (fetal alcohol syndrome), viral infection (rubella) and/or inadequate dietry folate intake (neural tube defects). These effects may also not be seen as a direct effect on a system or systems but result in a reduced birth weight and the potential postnatal developmental effects. Consider also this in relation to the increasing support to the fetal origins hypothesis.

Use the page links below to explore specific teratogens.

Environmental Links: Introduction | low folic acid | iodine deficiency | Nutrition | Drugs | Australian Drug Categories | USA Drug Categories | thalidomide | herbal drugs | Illegal Drugs | smoking | Fetal Alcohol Syndrome | TORCH | viral infection | bacterial infection | fungal infection | zoonotic infection | toxoplasmosis | Malaria | maternal diabetes | maternal hypertension | maternal hyperthermia | Maternal Inflammation | Maternal Obesity | hypoxia | biological toxins | chemicals | heavy metals | air pollution | radiation | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Fetal Origins Hypothesis
Viral Links: viral infection | TORCH | cytomegalovirus | hepatitis | HIV | parvovirus | polio | rubella virus | chickenpox | Lymphocytic Choriomeningitis Virus | Zika virus | human papillomavirus | rotavirus | West Nile virus | varicella virus | vaccination | zoonotic infection | environment
Historic Embryology - Viral 
1941 Rubella Cataracts | 1944 Rubella Defects
Bacterial Links: bacterial infection | syphilis | gonorrhea | tuberculosis | listeria | salmonella | TORCH | Environmental | Category:Bacteria
Abnormality Links: abnormal development | abnormal genetic | abnormal environmental | Unknown | teratogens | ectopic pregnancy | cardiovascular abnormalities | coelom abnormalities | endocrine abnormalities | gastrointestinal abnormalities | genital abnormalities | head abnormalities | integumentary abnormalities | musculoskeletal abnormalities | limb abnormalities | neural abnormalities | neural crest abnormalities | placenta abnormalities | renal abnormalities | respiratory abnormalities | hearing abnormalities | vision abnormalities | twinning | Developmental Origins of Health and Disease |  ICD-11
Historic Embryology  
1915 Congenital Cardiac Disease | 1917 Frequency of Anomalies in Human Embryos | 1920 Hydatiform Degeneration Tubal Pregnancy | 1921 Anencephalic Embryo | 1921 Rat and Man | 1966 Congenital Malformations

Some Recent Findings

  • Nanoparticle-induced neuronal toxicity across placental barriers is mediated by autophagy and dependent on astrocytes[1] The potential for maternal nanoparticle (NP) exposures to cause developmental toxicity in the fetus without the direct passage of NPs has previously been shown, but the mechanism remained elusive. We now demonstrate that exposure of cobalt and chromium NPs to BeWo cell barriers, an in vitro model of the human placenta, triggers impairment of the autophagic flux and release of interleukin-6. This contributes to the altered differentiation of human neural progenitor cells and DNA damage in the derived neurons and astrocytes."
  • Dispensing of potentially teratogenic drugs before conception and during pregnancy: a population-based study[2] "To study the dispensing of potentially teratogenic drugs in the 12-month period before as well as during pregnancy in the Netherlands. Drug-dispensing information was identified from the PHARMO Database Network for the 12-month period before conception and during pregnancy. Drugs with either a Swedish FASS 'D' classification, an Australian ADEC or American FDA 'D' or 'X' classification were considered potentially teratogenic (n = 202). ...Five percent of the pregnancies received a potentially teratogenic drug during pregnancy and 0.66% received a drug from the risk category X. It may be possible to reduce these proportions when reasons for prescription have been explored." (More? Abnormal Development - Drugs | Australian Drug Categories | USA Drug Categories)
  • Teratogen Screening Using Transcriptome Profiling of Differentiating Human Embryonic Stem Cells[3] "Teratogens are substances that may cause defects in normal embryonic development while not necessarily being toxic in adults. Identification of possible teratogenic compounds has been historically beset by the species-specific nature of the teratogen response. To examine teratogenic effects on early human development we performed non-biased expression profiling of differentiating human embryonic and induced-pluripotent stem cells treated with several drugs; ethanol, lithium, retinoic acid, caffeine and thalidomide, which is known to be highly species specific. Our results point to the potency of specific teratogens and their affected tissues and pathways. Specifically, we could show that ethanol caused dramatic increase in endodermal differentiation, retinoic acid caused misregulation of neural development, and thalidomide affected both these processes. We thus propose this method as a valuable addition to currently available animal screening approaches."
  • Maternal exposure to multi-wall carbon nanotubes does not induce embryo-fetal developmental toxicity in rats.[4] "The results show that repeated oral doses of multi-wall CNTs (MWCNTs) during pregnancy induces minimal maternal toxicity and no embryo-fetal toxicity at 1,000 mg/kg/day in rats. The no-observed-adverse-effect level of MWCNTs is considered to be 200 mg/kg/day for dams and 1,000 mg/kg/day for embryo-fetal development. In this study, the dosing formulation was not analyzed to determine the degree of reaggregation (or not), nor were blood levels of CNT's measured in the dosed animals to verify or characterize absorption."
More recent papers
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Critical Periods of Development

When studying this topic remember the concept of "critical periods of development" that will affect the overall impact of the above listed factors, as outlined in the table below. This can be extended to the potential differences between prenatal and postnatal effects, for example with infections and outcomes.

Critical Periods of Human Development
Conceptus Embryonic development (weeks) Fetal period (weeks)
Early zygote.jpg Week2 001 icon.jpg Stage9 sem4c.jpg Stage13 sem1c.jpg Stage15 bf1c.jpg Stage17 bf1c.jpg Stage19 bf1c.jpg Stage23 bf1c.jpg
Stage2.jpg Heart
Upper limbs
Lower limbs
CSt3.jpg Palate
Week2 001 icon.jpg External genitalia
Loss Major abnormalities Functional and Minor abnormalities
  Critical Period Links: critical period | abnormal development | Critical Periods table | Image - Critical Periods table | Genital | Opioids | Neural | Thalidomide | Environmental


  1. Hawkins SJ, Crompton LA, Sood A, Saunders M, Boyle NT, Buckley A, Minogue AM, McComish SF, Jiménez-Moreno N, Cordero-Llana O, Stathakos P, Gilmore CE, Kelly S, Lane JD, Case CP & Caldwell MA. (2018). Nanoparticle-induced neuronal toxicity across placental barriers is mediated by autophagy and dependent on astrocytes. Nat Nanotechnol , , . PMID: 29610530 DOI.
  2. Zomerdijk IM, Ruiter R, Houweling LM, Herings RM, Straus SM & Stricker BH. (2015). Dispensing of potentially teratogenic drugs before conception and during pregnancy: a population-based study. BJOG , 122, 1119-29. PMID: 25316196 DOI.
  3. Mayshar Y, Yanuka O & Benvenisty N. (2011). Teratogen screening using transcriptome profiling of differentiating human embryonic stem cells. J. Cell. Mol. Med. , 15, 1393-401. PMID: 20561110 DOI.
  4. Lim JH, Kim SH, Shin IS, Park NH, Moon C, Kang SS, Kim SH, Park SC & Kim JC. (2011). Maternal exposure to multi-wall carbon nanotubes does not induce embryo-fetal developmental toxicity in rats. Birth Defects Res. B Dev. Reprod. Toxicol. , 92, 69-76. PMID: 21254368 DOI.




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Cite this page: Hill, M.A. (2024, April 12) Embryology Abnormal Development - Teratogens. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Teratogens

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G