2) Embryology and Teratology (Part I) Flashcards
What is teratogenesis?
The production of congenital birth defects in an embryo or fetus
What are malfunctions?
Non-reversible morphological defects present at birth
What are the three types of malfunctions?
- External malfunctions (e.g. cleft palate)
- Internal malfunctions (e.g. malfunction in an organ)
- Microscopically visible malfunction
What are congenital anomalies?
Present at birth
How many types of congenital anomalies are there? What can they range from?
- 200 types
- Range from physical abnormalities to fatality
Birth defects are present in what percentage of live births?
2-3%
What are deaths to birth defects primarily due to?
Structural and functional defects in vital organs
Structural and functional defects in which vital organs are particularly susceptible to cause death?
- CNS
- Respiratory system
- Heart
What is the leading cause of infant death in North America?
Birth defects
What are the three reasons that explain why birth defects are the leading cause of infant death in North America?
1) Improvements in obstetrical care
2) Increased medications and social drug use
3) Contribution of environmental contaminants to teratogenesis
How does the incidence of birth defects vary at two years old? Why?
- At two years old, the incidence increases from 4 to 6%
- Due to the discovery of internal organ defects, which may have been symptomless at birth
Birth defects account for more than ___ of all deaths in infants below a year old, and ___ of all deaths in children above 15 years old.
- 1/3
- 1/4
Around 20 to 25% of the causes of birth defects are due to what? How are they identified?
- Genetic causes and chromosomal aberrations
- Identified by a constellation of characteristics of defects that are present together
Which factors play a role in the development of birth defects, apart from genetic and chromosomal aberrations?
- Metabolic (maternal illnesses)
- Radiation
- Infection (maternal illnesses)
- Exposure to drugs or chemicals
What is the susceptibility of teratogenesis heavily influenced by?
The genetics of the mother and infant, as well as environmental factors
What percentage of human pregnancies result in a healthy, normal infant?
Less than 50%
What do anomalies occurring during the early stages of embryogenesis lead to?
An early miscarriage
What three outcomes may the formation of a zygote lead to?
1) Healthy pregnancy that comes to term
2) Pregnancy that comes to term with the formation of anomalies
3) Pregnancy that does not come to term
What is the largest contributor to an unsuccessful pregnancy?
Post-implantation losses
What are post-implantation losses?
If the uterus is not ready to receive the zygote, then the fertilized egg is shed along with uterine tissue during the following menstrual cycle
What occurs during the conception period of reproduction?
1) Conception is the formation of a zygote from the union of the ovum and sperm
2) Implantation of the zygote into the uterine wall
What occurs during organogenesis?
The division and differentiation of the ovum to form tissues and organs
When does organogenesis occur?
Weeks 3 to 8 during pregnancy
What is the teratogenic period?
The most susceptible period to birth defects
When is the teratogenic period?
17 to 57 days post-fertilization
When does the neural tube close?
Within 28 days of gestation, when most women do not know they are pregnant yet
What is necessary for women to be CAPABLE of becoming pregnant, and avoiding a neural tube defect?
Adequate nutrition, specifically folate, PRIOR to conception
For all women, there is a __-day period following ovulation.
14
What is the period of maximal cell division and differentiation? What is it also referred to as?
- The organogenic period
- The critical period of growth
What should occur by the end of the organogenic period?
The development of the major fetal structures should be completed
What are the two types of growth during pregnancy?
- Hyperplasia
- Hypertrophy
What is hyperplasia?
Increase in cell number
What is hypertrophy?
Increase in cell size
When does hyperplasia occur? What is it characterized by?
- Day 17 to 8 weeks following fertilization
- Maximum vulnerability to teratogenic effects
What does interference with hyperplasia (e.g. toxicity or nutrition deficiencies) result in?
In a permanent reduction in cell NUMBER, which cannot be compensated for later, even with proper nutrition
What occurs after the hyperplasia period?
- Hypertrophy and hyperplasia
- Then, hypertrophy alone
When does hypertrophy occur? What is it characterized by?
- 8 weeks following fertilization
- Risk for development of organ or biochemical malfunctions
What is ovulation?
Ovum is expelled by the ovary into the Fallopian tubes
How may poor nutrition and toxic exposure affect fertilization?
Can decrease gamete viability (sperm or ovum), which may lead to decreased fertility or poor cell division
What does the zygote produce as it begins to cleave? How?
- Increase in the number of cells (but no increase in volume)
- The zygote produces the morula
What does the morula produce as a cavity forms in its center? What is the cavity called?
- The cavity is called the blastocele
- The morula produces the blastocyst
What types of cells does the blastocyst contain? Where are they located?
- Embryoblasts (inside)
- Trophoblasts (outside)
What is the primary function of trophoblast cells?
They secrete proteolytic enzymes, which erode epithelial uterine lining, allowing for the creation of an implantation site for the blastocyst
When does the histiotrophic phase occur?
20 to 25 days after fertilization
What occurs during the histiotrophic phase?
- Fluid and nutrients are derived from the erosion of the uterine lining
- They are absorbed by trophoblast cells through phagocytosis to provide nutrients for the blastocyst
Why is the histiotrophic phase necessary?
Because there is no placenta or fetal circulation to provide the fetus with nutrients
The trophoblast forms a cord of cells that extend into the ____________ and attach to start forming the _________.
endometrium
placenta
When does the formation of a zygote occur?
In the first week after ovulation
What is the pre-implantation period characterized by?
- An increase in cell number
- NO increase in cell size
What are the possible effects of exposure to toxins during the pre-implantation period? Why?
- No effect, slight decrease in growth, or lethality
- As the fate of the cells has not yet been determined (pluripotent nature), providing them with great restorative capacity
- Also, there is a decreased exposure to toxins due to poorer accessibility of the conceptus (not yet attached to uterine wall)
What is the susceptibility of teratogens during the pre-implantation period?
Low susceptibility to teratogens, and few developmental abnormalities
Which cells within the blastocyst form an embryo?
- The embryoblasts form an embryo
- Trophoblast cells do NOT become an embryo
What occurs at day 14, following implantation?
The inner cell mass starts to differentiate into different types of cells, starting with the formation of the Henson’s node (invagination)
Where does the formation of Henson’s node occur? How does it move?
In the future cranial area of the ectoderm, which moves caudally (front to back) to form the primitive streak
When does gastrulation occur?
2 to 3 weeks
What is gastrulation characterized by? What is gastrulation?
- Cell migration through the primitive streak
- Process that gives rise to the three germ layers (ectoderm, mesoderm, endoderm)
What are examples of the ectoderm?
- Brain
- CNS
- Skin
What are examples of the mesoderm?
- Voluntary muscles
- Cardiovascular system
- Excretory system
What are examples of the endoderm?
- Digestive system
- Respiratory system
- Glandular organs
Which period is very susceptible to teratogens?
Gastrulation
Describe the process of neurulation.
- The ectoderm differentiates into the neural plate, forming the neural groove
- The edges of the neural groove connect, forming the neural tube
What occurs to neural crest cells during neurulation? What are neural crest cells?
Neural crest cells (precursor cells to the embryo’s CNS) segregate during neurulation
What are characteristics of the embryo at 27 to 29 days post-ovulation?
- The shape of the embryo is established, and the heart starts beating
- Major organ development begins
- The embryo is smaller than an inch, or an ounce
What occurs if the neural tube does not close?
- Degeneration of nerves
- The precursor cells that are supposed to become CNS cells are exposed to amnionic fluid, which may cause degeneration
What factors may cause a NTD at 27 to 29 days?
- Factors that interfere with cell division (creation of the neural groove)
- Factors that interfere with cell fusion (joining of the edges to form the neural tube)
The growth during the organogenesis period is solely ___________.
hyperplasia (increase in cell number, but not size)
What occurs during organogenesis?
- Cell proliferation
- Cell migration
- Cell-cell interactions
- Tissue remodeling
Is organogenesis susceptible to teratogens?
- VERY susceptible to teratogenesis
- There are periods of maximum susceptibility for each forming structure
What occurs at the 8th week of gestation?
- The conceptus is now considered a fetus
- All the essential internal and external structures are present
When does the placenta account for most nutrient needs of the fetus?
At the 8th week of gestation
What is the fetal growth period characterized? Which organs are characterized by differentiation?
- Tissue differentiation, growth, and physical maturation of the fetus occur
- Differentiation of the external genitalia
Is the fetal growth period susceptible to teratogens?
- Functional and growth abnormalities occur rather than morphological abnormalities (apart from the genitalia)
- CNS and reproductive anomalies, as well as behavioural and motor deficits
Which organs are primarily susceptible during the embryonic period?
- Central nervous system
- Heart
- Limbs
- Ears
- Eyes
The period of greatest susceptibility to teratogenesis is characterized by ___________ defects, while latter defects are ________ or __________.
morphological
physiological, functional
The spectrum of defects depends on the _______ of the teratogenic influence.
timing
What are the three classes of teratogens?
- Medications
- Social drugs (alcohol, cocaine, smoking)
- Environmental agents (solvents, pesticides, PCBs)
How may the type of teratogenic exposure be identified?
By the occurrence of symptoms associated with the agents used
What substance is responsible for the most fetal abnormalities?
Alcohol
Differentiate a premature infant and a small for gestational age infant.
- Premature infant may be the proper size for the number of weeks it has been in gestation
- Small for gestational age infant are small for the number of weeks that it has been in gestation
What type of drug is Dilantin? What defects does it result in?
- Anti-epilectic drug
- Fetal hydantoin syndrome
What type of drug is Thalidomide? What defects does it result in?
- Immunomodulatory drug
- Limb and ear abnormalities
What type of drugs are antineoplastic drugs? What defects do they result in?
- Chemotherapy drug
- Congenital abnormalities
What type of drug is Diethylstilbestrol? What defects does it result in?
- Endocrine disruptor
- Uterine and cervical defects
What type of drug is Dextromethorphan? What defects does it result in?
- Cough-suppressant
- CNS abnormalities
Why should women who are pregnant (or planning to become pregnant) verify with their physician prior to consuming any sort of drugs (prescribed or not)?
Because almost all medications cross the placental wall
What are the four factors contributing to the risk of developing a defect, following exposure to drugs?
1) Type of medication
2) Time of exposure
3) Individual variation
4) Length of time of exposure
What four factors or health states may result in teratogenesis?
1) High temperature or fever
2) Infectious diseases
3) Chronic diseases
4) Nutrient deficiency or excess through dietary and drug intake
What are the effects of excess iodide?
- Congenital goitre
- Mental and physical retardation
What are the effects of excess fluoride?
Spina bifida occulta
What are the effects of excess vitamin D?
- Facial abnormalities
- Mental retardation
What are the effects of excess vitamin A?
CNS abnormalities
What are the effects of an intake of 10 000 IU of vitamin A?
Increased risk of NTDs by 4.8
What is the risk of NTD development due to vitamin A intake associated with?
- The timing of intake
- The highest risk occurs during the first six weeks of pregnancy
What are the effects of protein deficiency?
Microcephaly, characterized by a small head and brain
What are the effects of vitamin A deficiency?
- Eye abnormalities and microcephaly
- The teratogenic effects of vitamin A excess and deficiency are similar
What are the effects of vitamin D deficiency?
- Fetal rickets
- Hypoplasia of tooth enamal
- Growth failure due to decreased calcium availability to the fetus
What are the effects of vitamin E deficiency? What lifestyle factor increases the risk of vitamin E deficiency?
- Congenital abnormalities
- Smoking (pro-oxidant) decreases body vitamin E stores, which creates non-specific birth defects and spontaneous abortions
What are the effects of vitamin K deficiency? What factor may increase the likelihood of vitamin K deficiency?
- Coumadin syndrome
- If anticoagulants are consumed
What are the effects of folate deficiency? What factors may increase the likelihood of folate deficiency?
- NTDs
- Poor diet, maternal drug intake, or a genetic susceptibility to abnormalities in folate metabolism
What are the effects of iodine deficiency? What are its characteristics?
Cretinism, which is a syndrome of mental and physical retardation, characterized by a potbelly, large tongue, and the facial characteristics of Down syndrome
What is the world leading cause of mental retardation?
Cretinism
What are the effects of copper deficiency? What may cause an increased risk in copper deficiency?
- Connective brain tissue defects
- Brain and bone abnormalities
- Copper-chelating drugs increase the risk of copper deficiency
What is Menkes kinky hair syndrome? What are the effects?
- Genetic inborn errors of copper metabolism
- Causes major developmental abnormalities in brain, bones, and blood vessels
According to animal studies, what do short periods of zinc deficiency cause? Why?
- NTDs
- As mothers cannot mobilize zinc in time to meet embryonic needs
What is acrodermatitis enterpathica? What is it associated with?
- Result of the inability to absorb zinc
- Characterized by rashes, hair loss, diarrhea, and poor growth
- Associated with an increased risk of birth defects and pregnancy complications
