Lecture 6- teratogens

Teratology term

Study of monsters

Teratogens discovered

1941- Rubella virus causes growth defects

1950- Frasier group in montreal showed relation b/w genes and environment and how some genes can make u suceptible to a teratogen - mice w cortisone affecting the cleft palate

1960- Thalidomide causing phocomelia and amelia

Rubella

Can cause congenitial rubella syndrome (CRS)

→ include deafness, heart disease, cataracts, glaucoma etc

cases have decreased due to vaccines

→ teratogenic during first 18 weeks of development because thats when major organs are forming not very teratogenic after

Cortisone

Affects studied on mice w different strains or genes for cleft palate formation and saw how cortisone affects each strain differently

Thalidomide

Teratogenic during 255-50 days of development

→ causes inhibition of angionesis ( formation of blood vessels)

→ limb defects, usually fatal

→ Drug banned in the states by frances o kelsey

malformation during development

1. webbing between fingers not fixed - syndactyl

2. extra fingers and toes: polydactyl

3. cleft palate formation doesnt fuse properly

4. spine bifida and ancephaly due to neural fold not closing

5. hypospadia: urethral opening not on penis but shaft

6. phycomelia and amelia due to complications w amniotic fluid and blood flow loss

Types of teratogens

1. Environmental factors

2. maternal health like if she has diabetes

3. drugs

4. viruses

5. physical objects like radiation

principles of teratogen

predict how much damage it can cause

1. stage in development

2. mode of infection

3. gene

4. dose and duration of effect

Critical periods of susceptibility

No effect in 1-3 weeks because implantation hadnt occurred yet→ kill the developing embryo or cells will get replaced

Major susceptibility: 3-8 weeks : Major organs formed like Heart, limbs and cleft palate

Susceptibility: 3rd to 9 month: affects alr developed organs and their ability to function so affects are seen after they are born like blindness, intellectual disabilities etc.

→ Ears, CNS, eyes, teeth and exteernal genitalia

pre-natal exposures of teratogens that can have long-term effects

1. THey increase time of suceptibility from 1st week of development to adolescence

2. example is lead, it accumulates and builds up and attacks you, mercury, anti-epileptic meds

3. harder to view as hey are slow acting

valproate

anti-epilectic med, cause intellectual disability eye folds and no philtrum

mercury- minamata bay

mercury dumped in minamata bay → ppl ate fish exposed to merc→ minamta diseaes → bb born w blindness, intellectual disability and cerebral palsy

FAS vs FASD

FAS: FETAL ALCOHOL SYNDROME → 0.5 -0.7% prevalence

→ Have growth defects

→ Brain development affected: intellectual disability

→ Facial dysmorphogenesis

Affected w either of these means u have FAS

FASD: fetal alcohol spectrum disorder→ 2.5-7% prevalence (more inclusive)

Illegal drugs

U cant see effects but the drugs build up in fetus and can be more addicted (rat study)

→ Impair memory, behavior and make u more angry

congenital effects of heart

shunts do not close properly can change direction of blood flow

chambers not form properly

truncus arteriosus

Congenital effects of chromosomes

Down syndrome: Trisomy 21, Sex trisomies, sex monosomies: turner syndrome

Trisomy 18 and 13 → extremely fatal

Caused by improper separation, drugs

cri du chat

Effect in chromosome 5 impact larynx formation, cry sounds like cats

Congenital effects due to genes

Autosomal dominant: acroplasia: short limb dwarfism, aperts system: cranial face malformation

Autosomal recessive: sickle cell anemia → hemoglobin defect, phocomelia

X-linked: Androgen insensivity: test isnt recognized by wolfiann ducts, Hemophilia: blood clots form

what to look for when screeningÉ

1. neural tube defects

2. CHromosomal abnormality and genetic mutations

3. aneuplopidy

Type os screening tests and what they do

1. Screening: Test sample from maternal fluid and maternal blood: test for neural tube defects

2. Diagnostic: Chorionic villi, amniotic fluid, fetal blood (Risk of miscarriage increases)

Ultra sound testing

2 done

1. First testing done in 11-14 weeks: first trimester→ test to see gestational age, if there are multiple gestations

2. Second testin done: 18-22 weeks: second trimester→ test to see if any abnormalities or deformities detected

AFP

Alphafetoprotein secreted by liver and tested in MSS along w hgC and estradiol and can point to risk in aneuploidy if low AFP and high hCG and estradiol

abnormally high levels of AFP: can be due to neural tube defect, abdonimal defect and multiple gestations

Nuchal translucency

Testing done to measure thickness of fluid in embryo’s neck can point to aneuploidy

comlicatiosn w diagnostic tests

Increased risk of miscarriage only reccomended if mother’s age is high and other complicatikons came up in other screenings

Types of diagnostic tests

Chorionic villi sampling: test for chromosomal abnormalities (10-12 weeks)

Amniocentis: test heartbeat while taking sample from amniotic fluid (14-16 weeks) centrifuging culturing and analyzing to check for risks

fetal blood samplin after 18 weeks

Types of fetal surgery

Spine bifida surgery: repair nerves that are exposed

fetal heart surgery: very rare and done to prevent bloackage and allow heart to form naturally and prevent hypoplastic left heart syndrome