Abnormal Development - Teratogens

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Educational Use Only - Embryology is an educational resource for learning concepts in embryological development, no clinical information is provided and content should not be used for any other purpose.

Introduction

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 Infections | Viral Infection | Bacterial Infection | Zoonotic Infection | Toxoplasmosis | Malaria | Maternal Diabetes | Maternal Hypertension | Maternal Hyperthermia | Maternal Inflammation | Maternal Obesity | Hypoxia | Biological Toxins | Chemicals | Heavy Metals | Radiation | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Fetal Origins Hypothesis
Viral Links: TORCH Infections | Cytomegalovirus | Hepatitis Virus | HIV | Parvovirus | Polio Virus | Rubella Virus | Chickenpox | Lymphocytic Choriomeningitis Virus | Zika Virus | Vaccination | Environmental
Bacterial Links: Syphilis | Gonorrhea | Tuberculosis | Listeria | TORCH Infections | Environmental | Category:Bacteria
Abnormality Links: Introduction | Genetic | Environmental | Unknown | Teratogens | Cardiovascular | Coelomic Cavity | Endocrine | Gastrointestinal Tract | Genital | Head | Integumentary | Musculoskeletal | Limb | Neural | Neural Crest | Renal | Respiratory | Placenta | Sensory | Hearing | Vision | Twinning | Developmental Origins of Health and Disease | ICD-10
Historic Embryology  
1915 Congenital Cardiac Disease | 1917 Frequency of Anomalies in Human Embryos | 1920 Hydatiform Degeneration Tubal Pregnancy | 1921 Anencephalic Embryo

Some Recent Findings

  • Dispensing of potentially teratogenic drugs before conception and during pregnancy: a population-based study[1] "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[2] "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. [3] "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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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: teratogen

Jiangwa Xing, Yue Cao, Yang Yu, Huan Li, Ziwei Song, Hanry Yu In Vitro Micropatterned Human Pluripotent Stem Cell Test (µP-hPST) for Morphometric-Based Teratogen Screening. Sci Rep: 2017, 7(1);8491 PubMed 28819231

Josef Seifert Embryo yolk sac membrane kynurenine formamidase of l-tryptophan to NAD(+) pathway as a primary target for organophosphorus insecticides (OPI) in OPI-induced NAD-associated avian teratogenesis. Toxicol In Vitro: 2017; PubMed 28782636

Mark A Clapp, Sarah N Bernstein Preconception Counseling for Women With Cardiac Disease. Curr Treat Options Cardiovasc Med: 2017, 19(9);67 PubMed 28780659

Justine Benevent, Francois Montastruc, Christine Damase-Michel The importance of pharmacoepidemiology in pregnancy-implications for safety. Expert Opin Drug Saf: 2017;1-10 PubMed 28777918

Jean-Luc Boudenne, Julien Parinet, Carine Demelas, Tarek Manasfi, Bruno Coulomb Monitoring and factors affecting levels of airborne and water bromoform in chlorinated seawater swimming pools. J Environ Sci (China): 2017, 58;262-270 PubMed 28774617

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.


Dark Orange = major abnormality | Light Orange = minor abnormality


Conceptus Embryonic development (weeks) Fetal period (weeks)
1
2
3
4
5
6
7
8
9
16
20-36
38
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
Neural
Stage2.jpg Heart
Upper limbs
Lower limbs
Ear
Eye
CSt3.jpg Palate
Teeth
Week2 001 icon.jpg External genitalia
Loss Major abnormalities Functional and Minor abnormalities



'
Dark Orange = major abnormality | Light Orange = minor abnormality

References

  1. Im Zomerdijk, R Ruiter, Lma Houweling, Rmc Herings, Smjm Straus, Bh Stricker Dispensing of potentially teratogenic drugs before conception and during pregnancy: a population-based study. BJOG: 2014; PubMed 25316196
  2. Yoav Mayshar, Ofra Yanuka, Nissim Benvenisty Teratogen screening using transcriptome profiling of differentiating human embryonic stem cells. J. Cell. Mol. Med.: 2011, 15(6);1393-401 PubMed 20561110
  3. Lim JH, Kim SH, Shin IS, Park NH, Moon C, Kang SS, Kim SH, Park SC, Kim JC. Maternal exposure to multi-wall carbon nanotubes does not induce embryo-fetal developmental toxicity in rats. Birth Defects Res (Part B) 92:69-76, 2011. PMID:21254368

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Cite this page: Hill, M.A. 2017 Embryology Abnormal Development - Teratogens. Retrieved August 23, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Teratogens

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© Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G