Abnormal Development - Teratogens: Difference between revisions
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==Introduction== | ==Introduction== | ||
[[File:Human-critical_periods_of_development.jpg|thumb|350px|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''' | * '''Infections''' collectively grouped under the acronym [[Abnormal Development - TORCH Infections|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 diet''' the best characterised is the role of [[Abnormal Development - Folic Acid and Neural Tube Defects|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 [[Abnormal Development - Iodine Deficiency|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) | * '''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 [[Developmental Signals - Retinoic acid|retinoic acid]]. | ||
* '''Environment''' (smoking, chemicals, heavy metals, radiation) and maternal endocrine function (maternal diabetes, thyroid development) and maternal stress. | * '''Environment''' ([[Abnormal_Development_-_Smoking|smoking]], [[Abnormal Development - Chemicals|chemicals]], [[Abnormal Development - Heavy Metals|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'''. | * '''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}} | |||
{{Viral Links}} | |||
{{Bacterial Links}} | |||
{{Abnormality Links}} | |||
== Some Recent Findings == | == Some Recent Findings == | ||
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* '''Dispensing of potentially teratogenic drugs before conception and during pregnancy: a population-based study'''<ref name=PMID25316196><pubmed>25316196</pubmed></ref> "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'''<ref><pubmed>20561110</pubmed></ref> "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.''' <ref>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. [http://www.ncbi.nlm.nih.gov/pubmed/21254368 PMID:21254368]</ref> "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." | |||
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Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=teratogen ''teratogen''] | |||
<pubmed limit=5>teratogen</pubmed> | |||
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==Critical Periods of Development== | ==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. | |||
<center>'''<font color=orangered>Dark Orange = major abnormality</font> | <font color=orange>Light Orange = minor abnormality</font>'''</center> | |||
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==References== | ==References== | ||
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Revision as of 10:01, 13 December 2016
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Introduction
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.
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 | ||
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Some Recent Findings
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More recent papers |
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This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: teratogen <pubmed limit=5>teratogen</pubmed> |
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.
Conceptus | Embryonic development (weeks) | Fetal period (weeks) | |||||||||||||||||
Neural | |||||||||||||||||||
Heart | |||||||||||||||||||
Upper limbs | |||||||||||||||||||
Lower limbs | |||||||||||||||||||
Ear | |||||||||||||||||||
Eye | |||||||||||||||||||
Palate | |||||||||||||||||||
Teeth | |||||||||||||||||||
External genitalia | |||||||||||||||||||
Loss | Major abnormalities | Functional and Minor abnormalities |
'
References
- ↑ <pubmed>25316196</pubmed>
- ↑ <pubmed>20561110</pubmed>
- ↑ 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
Journals
- Birth Defects Research Part A: Clinical and Molecular Teratology
- Birth Defects Research Part B: Developmental and Reproductive Toxicology
- Part C: Embryo Today: Reviews
Reviews
Articles
Search Pubmed
Search Pubmed: teratogen | teratogenesis
Glossary Links
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Cite this page: Hill, M.A. (2024, April 24) Embryology Abnormal Development - Teratogens. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Teratogens
- © Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G