Lecture 3: Development and Teratogenesis Flashcards
3 stage human development
- Pre-embryonic period: fertilization through implantation
- embryonic period: implantation through gestational week 8
- fetal period: week 8 - birth (parturition)
Pre-Embryonic period (3)
- fertilization through implantation
- 3-4 days after fertilization, morula reached uterus
- 3-4 days after reaching uterus
- fluid cumulated creating blastocyst (hollow sphere of cells)
Embryonic period (3)
implantation-week 8
- 7 days after fertilization. blastocysts attached to uterine wall
- trophoblast secretes enzymes the digest endometrial cells - by day 14 uterine endometrium grows over blastocyst, enclosing it, and walling it off from the rest of the uterine cavity
- eventually: endometrium and embryonic trohpblast will combiner’s to form placenta
- later of cells will separate to form the amnion, and cavity that results with fluid
Fetal period (5)
week 8-birth (parturition)
- end of week 8: all major organs formed but not complete
- fetus undergoes period of growth and maturation
- divided into trimesters
- ends a birth
- organ development, change in body proportions
Blastocyst
- hollow sphere of cells
Inner cell mass
forms within blastocyst
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will become embryo
-ectoderm
-mesoderm
-endoderm
3 layers give rise to organ
~~~
trophoblast
will become embryonic portion of placenta
Organogenesis
ecto/endo/meso
give rise to organs
tetralogy
scientific study of congenital abnormalities and abnormal formations
Modern tetralogy
- emerged as science in 1930s with studies on pigs
- pig deficient in vitamin A are born with malformations including lack of eyes
Teratogen (5)
- any agent that can produce a congenital anomaly or raise the incidence of anomaly in population
- have potential to affect the normal development of human embryo following maternal exposure
- typically environmental: drugs, chemicals, radiation, functional, metabolic, behavior abnormality
- effect varies from death to embryo-structural, functional, metabolic, and behavioral abnormality
- results in developmental disorders at birth termed birth defects, congenital anomalies, or congenital malformations
Capacity of agent to produce birth defects depends on (6)
- developmental stage at the time of exposure
- dose and duration of exposure
- genotype of emberyo
- MOA - specific, may involve inhibition of specific biochemical or molecular process
- cell death
- decreased cell proliferation
- other cellular phenomena - access of adverse influences to developing tissues depends on nature of agent
Manifestations of abnormal development (4)
- death
- malformation
- growth retardation
- functional d/o
Effects of teratogens in pre-embryonic period (2)
- kills embryo
- spontaneous abortion, goes unnoticed
OR
- disrupted effects are compensated for by the early embryo
Effect teratogens in embryonic period (1)
- most sensitive period for inducing major birth defects
Effect teratogens in fetal period (1)
- teratogen damage unlikely to produce malformations but can cause
- death
- growth retardation
- disruptions or functional defects
Thalidomide
initial use
used today
issues
- 1950s, for treatment of pregnancy assoc. morning sickness
- taken off market for SE
- stunted limb growth
- blindness
- disfigurement
- cleft palate
- other internal disability’s - used today to tx illness
- multiple myeloma
- erythema nodosum
- leprosum
- HIV wasting
- apthous ulcers
phocomelia
stunted growth limbs, hands and feet attacked close to body
-flippers of seal resemblance
TORCH infections
T oxoplasmosis/toxoplasma gondii
O other infections
R ubella
C cytomeglavirus
H herpex simplex virus 2
Other= coxsackievirus, syphillis, varicella zoster, HIV, parvovirus B19, hep B
- can cross placenta
TORCH Complex effects (7)
- fever
- difficulties feeding
- small areas bleeding under skin
- enlargement of liver and spleen
- jaundice
- hearing impariment
- abnormalities of eyes
Fetal Alcohol Syndrome (7)
- behavior distrubances
- brain defects
- low IQ - cardiac defects
- spinal defects
- cranoifacial anomalies
- co-morbid conitions
- mental retardation
- ADHD
- learning d/o
- sensory impairment
- cebral palsy
- epilepsy - fetal alcohol effect: children who don’t exhibit entire spectrum of abnormalities
Teratogens in cigarette smoke (8)
- nicotine
- cotinine
- cyanide
- thiocyanate
- carbon monoxide
- cadmium
- lead
- hydrocarbons
effects of teratogens in cigarette smoke (4)
- fetotoxic
- vasoactive effects-reduce oxygen levels
- low birth weight
- assoc. with increase of sub fertility, spontaneous abortion, placenta prevue, abruption, preterm delivery
Cocaine(4)
- local vasoconstriction and hypertensive properties
- maternal complications
- MI
- arrythmias
- aoritc rupture
- stroke
- seizure
- bowel ischemia
- sudden death - exposed embryo at higher rx for placental abruption
- high rx still birth because of vascular disruption
- highest rx after first trimester
Cocaine congenital anomalies results from vascular disruption (6)
- skull defects
- cutis aplasia
- poencephaly
- subependymal and periventricular cyts - ileal atresia
- cardiac anomomalies
- visceral infarcts
Methamphetamine (4)
- assoc. with low birth weight
- small gestational age (SGA)
- increased rx for neurodevelopment problems
- results confunded bc pts. use multiple drugs *
Heroin (4)
- no specific teratogenic potential found
- assoc. with malnutrition of mother and lack of prenatal care
- assoc. with use of other illicit drugs with teratogenic potential
- assoc. with neonatal abstinence syndrome (NAS)
Excessive intake vitamin A
- avoid unnecessary supplementation in women of childbearing age
- can cause malformations involving
- cranium
- face
- heart
- CNS
- thymus - isotretinoin
- 1st trimester exposure: fetal loss
- 26 fold increased malformation rate in survivors is similar to that of children exposed to thalidomide
Diethylstilbesterol (DES)
- once used to support hight-rx pregnancy
- DES exposed women have 2-fold increase in vaginal and cevical intraepithelial neoplasia
- 1/4 th exposed females have structural abnormalities of cervix or vagina
- affected women at increased rx poor pregnancy outcome
- exposed male fetuses have normal sexual function and fertility but are at increased rx for epididymal cysts, mirophallus, cryptorchidism, testicular hyperplasia, and hposapadias
Exposed female fetus vaginal abnormalities from DES
- hypopastic t-shpates uterine cavity
- cervical collars
- woods, septa, coxcombs
- withered fallopian tubes
