Teratogens Flashcards
congenital defects
- Refers to all inborn abnormalities, morphological or biochemical at birth
- Measurable effect on physical, intellectual, and social wellbeing
- ~50-80 % of conceptuses lost before implantation
- > 50% miscarriages due to chromosomal structural abnormalities
- ~2% of all pregnancies terminate in stillbirths
- Congenital defects found in 6% of all liveborn infants examined during the first year of life
causes of congenital defects
Environmental factors
o Infectious Agents
o Chemical & Pharmacological
o Radiation
Genetic defects
o Chromosomal
o Monogenic
Idiopathic
congenital anomalies - birth defects
Most common birth defects are: o heart defects o cleft lip/cleft palate o down syndrome o spina bifida
teratogens - environmental factors
Teratogen – any agent that can harm an embryo or fetus
- Effects depend on:
o Critical period of development (structures forming)
o Dosage and duration of exposure of drug/chemical
o Father’s exposure may affect embryo
o Genotype of mother and embryo
o Same defect can get caused by different teratogens
o One teratogen can cause different defects
o Long-term effects depend on postnatal environment
o Some effects not apparent until later in life
critical periods of prenatal development
Each organ or structure has a critical period when it is most sensitive to damage from teratogens. heart: wk 2.5-5.5 lower limb: wk 3.5-5.5 ear: wk 3.5-8.5 CNS: wk 3-16 eyes: wk 4.5-8.5 arms: wk4-6
rubella (infectious agent)
- Infectious viral disease caused by Rubella virus
- Causes mild infection in adults, but severe effects in fetuses
- Congenital rubella syndrome. –> miscarriage or birth defects including heart defects , deafness, brain damage, eye problems, cardiac abnormalities, mental retardation
- Most dangerous during 1st trimester (40-60% chance of affected fetus)
- No woman should try to conceive unless they have had rubella or have been immunized!
- Women planning a pregnancy –> blood test, to check sufficient antibody titers against rubella present
toxoplasmosis (infectious agent)
- A zoonotic intracellular parasitic infection caused by Toxoplasma gondii (a protozoan)
- Carried by many mammals: rabbits, dogs with, but final host = cats
- Caused by eating undercooked/contaminated meat (avoid cold cured meats including salami, parma ham, chorizo and pepperoni), handling cat feces
- Can cross the placenta -> can affect the brain (e.g. hydrocephalus, mental retardation) and impaired vision & blindness) during first trimester
- Induces miscarriage later in pregnancy
zika virus (infectious agent)
- Zika virus flavivirus
- Outbreaks recorded in Africa, the Americas, Asia and the Pacific
- Transmitted through the bite of an infected aedes arthropods (mosquitoes)
- Symptoms generally mild and include fever, rash, conjunctivitis, muscle and joint pain , malaise or headache
Congenital zika syndrome - Zika virus can be transmitted from mother to fetus during pregnancy
Congenital Zika syndrome: Infection during pregnancy -> can cause infants to be born with microcephaly and other congenital malformations
- Zika infections in pregnant women also have been linked to miscarriages and stillbirth
- In CT scans of infants -> calcifications in brain tissue
listeria and salmonella (infectious agent)
Listeria:
- Listeria bacteria -> infection called listeriosis
- Pregnant women advised not to eat any uncooked mould-ripened soft cheese (brie, camembert), raw seafood (oysters, sashimi, sushi), smoked ready-to-eat seafood and cooked ready-to-eat prawns
- Listeria infection during pregnancy can cause miscarriage, stillbirth or severe illness in newborns
Salmonella:
- Salmonella bacteria -> can cause gastroenteritis or food poisoning
- Avoid foods that contain raw and undercooked eggs (poached,
- homemade mayonnaise), or reheated chicken
thalidomide (Chemical and Pharmacological Teratogens)
- 1950-1960: To prevent nausea and vomiting = morning sickness
- Tested on animals and was deemed “safe”
- Can cause severed birth defects if taken during first 2 months of pregnancy
- Phocomelia: fetus with hands and feet without arms or legs
- Ectromelia: total absence of limbs
- Malformation of eyes, ears, noses, hearts, thumbs
alcohol (Chemical and Pharmacological Teratogens)
- Compromises functioning of the placenta
- Can easily cross placenta –> adversely affects fetal development
- Chronic alcohol abuse can result in fetal alcohol syndrome (30-45%)
Fetal alcohol syndrome (FAS)
- Microcephaly, malformation of heart, limbs, joints and face, hyperactivity, seizures, tremor, lower IQ, major adjustment problems, slow physical growth, poor motor skills, attention difficulties, verbal learning difficulties
cigarette smoking (Chemical and Pharmacological Teratogens)
- Cleft lip
- Abnormal lung functioning
- Miscarriage
- Low-birth-weight
- Ectopic pregnancy –> implantation in fallopian tube
- Sudden Infant Death Syndrome
- Higher concentration of nicotine in foetus
radiation
- Radiation – death, mental retardation
- Severity differs depending on stage of pregnancy and absorbed dose
- Most significant during organogenesis
- 25 % of surviving children born at the time of atomic bomb explosion over Hiroshima & Nagasaki had CNS abnormalities (microcephaly & mental retardation)
- Relative risk of leukaemia and cancer may be as high as 1.4 –> Avoid X-rays during pregnancy
alterations in chromosome structure
Only very few compatible with live birth - Often associated with cancer o Deletions o Duplications o Translocations o Inversions
deletions
- Cri du chat (cry of the cat):
- Deletion of a small portion of chromosome 5
- Children have severe mental impairment, a small head with unusual facial features, and a cry that sounds like a distressed cat
duplications
- Fragile X Syndrome:
- Affects 1:1500 males, 1:2500 females
- Often associated with intellectual disability
- Expansion of the CGG trinucleotide repeat affecting the Fragile X mental retardation 1 (FMR1) gene on the X chromosome
- Most people 29 repeats , Fragile X > 700 repeats due to duplications –> failure in correct protein expression required for normal neural development
translocations
- Fragment of a chromosome is moved (“trans-located”) from one chromosome to another
- Balance of genes is still normal i.e. no genetic material has been gained or lost
- Transcription of genes can be altered
- Can cause cancer if placed in front of promotor of growth regulating gene
Acute Myeloid Leukemia (AML)
- Translocation t(15/17)
- Affects ~ 4:100,000 Australians
- Leukemias starting in the myeloid cell line
- Rapid growth of poorly differentiated white blood cells. –> accumulate in the bone marrow
- Often inadequate production of red blood cells and platelets -> anaemia, easy bleeding & bruising
- Immature –> unable to function properly to prevent or fight infection
inversions
- Chromosome breaks in 2 places –> broken piece flips then re-inserts back to front
- Does not involve loss or gain of chromosomal material
- Protein expression might be affected
- Inversion on chromosome 9 is most common but does not cause disease
- In Hemophilia A, 40% of mutations due to Inversions
what is a teratogen
agent that induces or increase incidence of a congenital malformation
what is a congenital malformation
Inborn abnormality, morphological or biochemical at birth
Malformations that effect noate at birth
most common 4 malformations in a baby
- Heart defects
- Cleft lip/cleft palate
- Down syndrome
- Spinda bifida
Why is the embryo/fetus most vulnerable to teratogens up to the third month?
major structural abnormalities coincide embryonic period – during organogenesis so why most vulnerable, after that period – more physiological changes
categories of environmental factors that cause congenital malformations
Infectious agents, chemical and pharmacological, radiation, malnutrition (less environmental)
what does idiopathic mean
relating to or denoting any disease or condition for which the cause/origin is unknown
3 infectious agents that cause congenital malformations
Rubella virus –> rubella
Toxoplasma gondii –> toxoplasmosis
Zika virus flavivirus –> zika virus
thalidomide causes
Phocomelia: foetus with hands and feet without arms or legs
Ectromelia: total absence of limbs
Malformation of eyes, ears, noses, hearts, thumbs
