Lecture 3: Development and Teratogenesis

Question 1

3 stage human development

Answer 1

1. Pre-embryonic period: fertilization through implantation
2. embryonic period: implantation through gestational week 8
3. fetal period: week 8 - birth (parturition)

Question 2

Pre-Embryonic period (3)

Answer 2

1. fertilization through implantation
2. 3-4 days after fertilization, morula reached uterus
3. 3-4 days after reaching uterus
   - fluid cumulated creating blastocyst (hollow sphere of cells)

Question 3

Embryonic period (3)

Answer 3

implantation-week 8

1. 7 days after fertilization. blastocysts attached to uterine wall
   - trophoblast secretes enzymes the digest endometrial cells
2. by day 14 uterine endometrium grows over blastocyst, enclosing it, and walling it off from the rest of the uterine cavity
3. 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

Question 4

Fetal period (5)

Answer 4

week 8-birth (parturition)

1. end of week 8: all major organs formed but not complete
2. fetus undergoes period of growth and maturation
3. divided into trimesters
4. ends a birth
5. organ development, change in body proportions

Question 5

Blastocyst

Answer 5

1. hollow sphere of cells

Question 6

Inner cell mass

Answer 6

forms within blastocyst

```
will become embryo
-ectoderm
-mesoderm
-endoderm
3 layers give rise to organ
~~~

Question 7

trophoblast

Answer 7

will become embryonic portion of placenta

Question 8

Organogenesis

Answer 8

ecto/endo/meso

give rise to organs

Question 9

tetralogy

Answer 9

scientific study of congenital abnormalities and abnormal formations

Question 10

Modern tetralogy

Answer 10

1. emerged as science in 1930s with studies on pigs

- pig deficient in vitamin A are born with malformations including lack of eyes

Question 11

Teratogen (5)

Answer 11

1. any agent that can produce a congenital anomaly or raise the incidence of anomaly in population
2. have potential to affect the normal development of human embryo following maternal exposure
3. typically environmental: drugs, chemicals, radiation, functional, metabolic, behavior abnormality
4. effect varies from death to embryo-structural, functional, metabolic, and behavioral abnormality
5. results in developmental disorders at birth termed birth defects, congenital anomalies, or congenital malformations

Question 12

Capacity of agent to produce birth defects depends on (6)

Answer 12

1. developmental stage at the time of exposure
2. dose and duration of exposure
3. genotype of emberyo
4. MOA - specific, may involve inhibition of specific biochemical or molecular process
   - cell death
   - decreased cell proliferation
   - other cellular phenomena
5. access of adverse influences to developing tissues depends on nature of agent

Question 13

Manifestations of abnormal development (4)

Answer 13

1. death
2. malformation
3. growth retardation
4. functional d/o

Question 14

Effects of teratogens in pre-embryonic period (2)

Answer 14

1. kills embryo
   - spontaneous abortion, goes unnoticed

OR

2. disrupted effects are compensated for by the early embryo

Question 15

Effect teratogens in embryonic period (1)

Answer 15

1. most sensitive period for inducing major birth defects

Question 16

Effect teratogens in fetal period (1)

Answer 16

1. teratogen damage unlikely to produce malformations but can cause
   - death
   - growth retardation
   - disruptions or functional defects

Question 17

Thalidomide

initial use
used today
issues

Answer 17

1. 1950s, for treatment of pregnancy assoc. morning sickness
2. taken off market for SE
   - stunted limb growth
   - blindness
   - disfigurement
   - cleft palate
   - other internal disability’s
3. used today to tx illness
   - multiple myeloma
   - erythema nodosum
   - leprosum
   - HIV wasting
   - apthous ulcers

Question 18

phocomelia

Answer 18

stunted growth limbs, hands and feet attacked close to body

-flippers of seal resemblance

Question 19

TORCH infections

Answer 19

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

Question 20

TORCH Complex effects (7)

Answer 20

1. fever
2. difficulties feeding
3. small areas bleeding under skin
4. enlargement of liver and spleen
5. jaundice
6. hearing impariment
7. abnormalities of eyes

Question 21

Fetal Alcohol Syndrome (7)

Answer 21

1. behavior distrubances
2. brain defects
   - low IQ
3. cardiac defects
4. spinal defects
5. cranoifacial anomalies
6. co-morbid conitions
   - mental retardation
   - ADHD
   - learning d/o
   - sensory impairment
   - cebral palsy
   - epilepsy
7. fetal alcohol effect: children who don’t exhibit entire spectrum of abnormalities

Question 22

Teratogens in cigarette smoke (8)

Answer 22

1. nicotine
2. cotinine
3. cyanide
4. thiocyanate
5. carbon monoxide
6. cadmium
7. lead
8. hydrocarbons

Question 23

effects of teratogens in cigarette smoke (4)

Answer 23

1. fetotoxic
2. vasoactive effects-reduce oxygen levels
3. low birth weight
4. assoc. with increase of sub fertility, spontaneous abortion, placenta prevue, abruption, preterm delivery

Question 24

Cocaine(4)

Answer 24

1. local vasoconstriction and hypertensive properties
2. maternal complications
   - MI
   - arrythmias
   - aoritc rupture
   - stroke
   - seizure
   - bowel ischemia
   - sudden death
3. exposed embryo at higher rx for placental abruption
4. high rx still birth because of vascular disruption
   - highest rx after first trimester

Question 25

Cocaine congenital anomalies results from vascular disruption (6)

Answer 25

1. skull defects
2. cutis aplasia
3. poencephaly
   - subependymal and periventricular cyts
4. ileal atresia
5. cardiac anomomalies
6. visceral infarcts

Question 26

Methamphetamine (4)

Answer 26

1. assoc. with low birth weight
2. small gestational age (SGA)
3. increased rx for neurodevelopment problems
4. results confunded bc pts. use multiple drugs *

Question 27

Heroin (4)

Answer 27

1. no specific teratogenic potential found
2. assoc. with malnutrition of mother and lack of prenatal care
3. assoc. with use of other illicit drugs with teratogenic potential
4. assoc. with neonatal abstinence syndrome (NAS)

Question 28

Excessive intake vitamin A

Answer 28

1. avoid unnecessary supplementation in women of childbearing age
2. can cause malformations involving
   - cranium
   - face
   - heart
   - CNS
   - thymus
3. isotretinoin
   - 1st trimester exposure: fetal loss
   - 26 fold increased malformation rate in survivors is similar to that of children exposed to thalidomide

Question 29

Diethylstilbesterol (DES)

Answer 29

1. once used to support hight-rx pregnancy
2. DES exposed women have 2-fold increase in vaginal and cevical intraepithelial neoplasia
3. 1/4 th exposed females have structural abnormalities of cervix or vagina
4. affected women at increased rx poor pregnancy outcome
5. exposed male fetuses have normal sexual function and fertility but are at increased rx for epididymal cysts, mirophallus, cryptorchidism, testicular hyperplasia, and hposapadias

Question 30

Exposed female fetus vaginal abnormalities from DES

Answer 30

1. hypopastic t-shpates uterine cavity
2. cervical collars
3. woods, septa, coxcombs
4. withered fallopian tubes