Reproduction 3 - Abnormalities in Human Development Flashcards
1
Q
List causes of mal-development
A
- 30% genetic
- 15% environmental
- 55% multifactorial
2
Q
How do idential twins form?
A
- One conceptus forms 2/3 inner cell masses to form 2/3 genetically identical individuals
- Splitting very early on in development
3
Q
What is chimerism?
A
- Where 2 genetically distinct conceptuses combine to form one individual
- Blaschkos lines (skin patches due to rhe reaction to two sets of DNA)
4
Q
List types of cellular distributions
A
- Mosaicism (non-disjunction) where there are differences between cells within one individual (eg. different eye colours)
- Distribution of cells between inner cell mass and trophectoderm (placenta)
- Chimerism - fuzed multiple zygotes
5
Q
Describe eye colour genetics and differentiation
A
- Human chromosome 15
- Brown is the most common
- Differentiation of eyes begins about day 22
- Event must predate day 22
6
Q
List possible chromosomal problems
A
- Too many (addition of part of the gene has less of an impact than complete trisomy)
- Too few
- Translocations
- All give rise to syndromes
7
Q
Give examples of XY linked disorders caused by increased numbers of chromosomes
A
- Kleinfelters XXY (decreased fertility)
- XXYY, XXXY, XXXYY related to Kleinfelters
- XYY (and XXYY) taller and learning problems
- XXX limited effects, some mental changes
- XXXX, XXXX more severe effects
8
Q
Give examples of autosomal disorders caused by too many chromosomes
A
- Downs syndrome chromosome 21 (cardiac problems determines survival)
- Edwards syndrome chromosome 18 (live less than 2 weeks)
- Pataus syndrome chromosome 13 (live for a year)
- Pregnancy is not viable in all other trisomes
9
Q
List XY linked diseases related to too few chromosomes
A
- Turners syndrome (female, short stature, infertile)
- Y0 not viable
10
Q
List autosomal disorders related to twoo few chromosomes
A
- No complete losses are viable
- Partial chromosome loss syndromes are possible
11
Q
What are translocations related to?
A
- Altered distribution
- XY translocation makes an XX male (genetically female but phenotypically male, one X chromosome contains DNA from a Y chromosome)
- Development of tumours
- Lymphoma, leukaemia and sarcoma
12
Q
What is achondroplasia?
A
- Gain of function mutation in FGFR3
- Defect in conversion of cartilage to bone and lack of bone growth
13
Q
How frequent are abnormalities in pregnancies?
A
- Major abnormalities occur in 3% of pregnancies, responsible for 25% of infant deaths
- Minor abnormalities occur in 15% of pregnancies, they have little health impact
14
Q
Define teratogen
A
Any agent that can disturb the development of an embryo or fetus. (Infectious agents, physical agents, and chemical agents)
15
Q
List infectious teratogens
A
- Rubella virus - Cataracts, glaucoma, heart defects, deafness, teeth
- Herpes simplex virus - Microphthalmia, microcephaly, retinal dysplasia
- HIV - Microcephaly, growth restriction
- Syphilis - Mental retardation, deafness
- Zika virus – microcephaly
16
Q
List physical agent teratogens
A
X-rays & other ionising radiation - Microcephaly, spina bifida, cleft palate, limb defects
17
Q
List chemical agent teratogens
A
- Thalidomide - Limb defects, heart malformations
- Lithium - Heart malformations
- Amphetamines - Cleft lip and palate, heart defects
- Cocaine - Growth restriction, microcephaly, behavioral abnormalities
- Alcohol - Fetal alcohol syndrome, maxillary hypoplasia, heart defects
18
Q
Describe limb development in the foetus
A
- Forelimb bud appears at day 27/8
- Hindlimb bud at day 29
- Grow out from lateral plate mesoderm rapidly under control of special signalling regions (fibroblast like growth factors). Differentiation to give digits.
- Fully formed and patterned by day 56.
- Zone of polarising activity determines the pattern of development of the digits (control centre)
- Sonic hedgehog gene controls pattern of digit development
19
Q
What is anencephaly?
A
- Defect in skull and brain development
- Incidence: 1 – 8 per 10,000 births
- Female babies affected more commonly than male
20
Q
How can anencephaly be prevented?
A
Folic acid - similar causes to spina bifida
21
Q
List effects of thalidomide
A
- 10,000 affected infants known, ~50% initial survival rate.
- Limbs primarily affected.
- In addition, deformed eyes and hearts, deformed alimentary and urinary tracts, blindness and deafness.
- Used now to treat some leprosy and cancer treatments (may be given to women of reproductive age)
22
Q
What is respiratory distress syndrome?
How is it treated?
A
- 1% of all births
- Occurs in preterm infants who have low levels of surfactant
- Therefore, delaying birth of a preterm infant allows more time for surfactant to be produced
- Injection of glucocorticoids (24-48 hours) can also accellerate formation
- Artificial surfactant has been developed
23
Q
When do conjoined twins form?
A
Incomplete inner cell mass separation, causing identical twins to be joined by their bodies
24
Q
What is the consequence of mutation in TBX5?
A
- Heart does not properly form 4 chambers, and so becomes oversized due to having to work harder than usual
- Causes a range of hand abnormalities (5 digits, abnormal thumbs, or a thumb of the same structure of a finger, not opposable)
25
What is a birth defect?
- Same as congenital malformation/ congenital abnormality
| - Changes in pattern of development (teratology/ dysmorphology)
26
Give examples of mal-development
- Extra fingers (polydactyl)
- Spina bifida
- Cleft lip/ palate
- Thalidamide
27
Describe facial development
- Face develops in two halves at the side of the head. Eyes develop at the level of the ears, and the nose where the eyes are
- Movement to the middle of the face
- Form over around 5 weeks until they reach their expected position, with movement of preexisting structures
- Repeated formation of clefts in the face and filling in of the clefts leads to sequential loss of tissue from the centre of the face, and movement of tissues to the correct places
28
How does cleft lip/palate occur?
- Clefts in the lip asymmetric, as only one of the two clefts is not functioning correctly
- Cleft in the palate symmetric as the halves of the palate do not meet and fuse correctly
29
How can cleft palate be treated?
- Modified by surgery
| - Turnover of cells in infants is rapid, so healing occurs with little scarring
30
How does spina bifida occur?
- Bulge of tissue from the spine, parralel tissues either side of the spine, often affecting the lower back and therefore lower limb
- May be just CSF or may contain neural tissue
- Spina bifida occulta is where there is a patch of hair where the defect is
- Fusion of the neural tube is not completed (neurulation).
31
How is spina bifida treated?
- Surgery placing skin to protect the neural tissue, though this does not repair the functional problems (eg. inability to walk)
- Effective treatment is mother taking folic acid during pregnancy, or 3 months before pregnancy as this is when the egg develops (70% decrease in incidence)
32
How common is spina bifida?
1-2 per 1000 pregnancies
33
What is anencephaly?
- Compromised development of the head and skull, incidence of 0.2/1000 births
- Lack of closure of the anterior neuropore
34
How does thalidamide work?
- Damages developing blood vessels, therefore depriving adjacent cells of nutrients and preventing proper growth and development
- Timing of administration (8 weeks onwards, limb ridge development at age 28) for morning sickness matched with upper limb development
- Upper limbs are particularly sensitive to thalidamide
35
Describe the development of the embryo
- Preimplantation occurs through the fallopian tube, characterised by cleavage divisions to produce a ball of undifferentiated cells (morula)
- This develops into a blastocyst with an outer layer of trophectoderm, an inner cell mass and a fluid-filled cavity
- Blastocyt hatches from the zona pellucida to implant in the uterine lining
- Inner cell mass becomes a bilayer disk (hypoblast and epiblast - gives rise to the human fetus)
- Gastrulation converts bilayer (epiblast and hypoblast) into a trilaminer embryo (ectoderm, mesoderm and endoderm) occuring days 14-18 postfertilisation
- Neurulation is initiated before gastrulation is complete (differentiation of the ectoderm to give the CNS)
- Folding of the embryo occurs laterally, fusing the ventral midline, and anterio-posteriorly which folds the primordial germ cell into the hind gut, and developing heart progenitors under the head of the embryo
- By week 4, all precursers have been layed down
- Urogenital, cardiac, facial and lung development all proceed rapidly during the second month as well as initial limb buds growing
- Cases 8 weeks post fertilisation (becomes a fetus)
36
What does the ectoderm layer form?
Skin and CNS
37
What does the mesoderm layer form?
- Muscles
- Blood
- Skeleton
- Heart
- Kidney
38
What does the endoderm layer form?
- Gut
- Lungs
- Liver
39
What happens primarily in the second and third trimester?
Growth
40
Describe the process of renal development
- Pronephros is the most immature form of kidney
- Mesonephros, an intermediate phase
- Metanephros is most developed and persists as the definitive adult kidney
- Ureters extend in length, retaining kidney bladder connections while the kidneys form new connections with the developing arterial system, with renal arteries forming and breaking down.
- The kidneys move superiorly and posteriorly (ascend) during development
41
Summarise the main events of gonadal development
- The gonads arise from intermediate mesoderm within the urogenital ridges of the embryo
- The genital ducts arise from paired mesonephric and paramesonephric ducts (formed from within the mesonephros)
- Gonad preecursor develops from the mesonephric mesoderm, covered by coelomic epithelial cells
- Primordial germ cells give rise to gametes (epiblast to caudal part of yolk sac, then migate to hind gut)
- Gonads show no differentiation in development until about 7 weeks of development
42
What is the difference between male and female reproductive system development?
- Differential development of the male reproductive system is dependent on the activity of sex-determining region Y (SRY) protein, coded for by the SRY gene on the Y chromosome.
- The mesonephric ducts give rise to male genital ducts
- The paramesonephric ducts give rise to female genital ducts
43
List the possible abnormalities of renal development
- One kidney may be retained in the pelvis
- Retention of an extra artery may obstruct the ureter and cause enlargement of the renal pelvis
- Kidneys may fuse to form a horseshoe kidney and remain in the pelvis
44
List the key regulators of male development
- Testosterone from the testes laydig cells, under stimulation of hCG
- Starts when hCG levels are at a peak
- anti-Mullerian hormone causes regression of the paramsonephric ducts
- Testosterone supports development of the wolffian ducts (gives rise to male reproductive tract)
45
List issues with development in reproductive system
- Inability to produce appropriate hormones or inability for target tissues to respond to these hormones
- Androgen insensitivity syndrome occurs in males with mutated androgen receptor. Testes do not descend, and there is limited virulisation
- Congenital adrenal hyperplasia can result in excess androgen production causing partial virulisation of the female
46
Describe the process of heart development
- Cardiogenic cells develop in a U shaped pattern outside of the embryo proper
- Forms a pair of heart tubes, which fuse to form a single heart tube by 21 days post-fertilisation (can pump blood unidirectionally)
- Looping and septation give rise to the 4 chamber structure
- During this, vascular connections are maintained and valves develop
- In the fetus foramen ovale allows blood to pass from right atrium to left atrium
- Ductus arteriosus connects pulmonary trunk to aorta to prevent blood going to the lungs
- These should close post birth
47
What is the teratology of fallot?
- Combination of 4 defects in the heart
- Pulmonary valve stenosis
- Thickened right ventricle wall
- Ventricular septal defect (allows deoxygenated blood into the left ventricle)
- Aorta overrides septal defect (misplaced aorta)
48
Describe defects in transposition of blood vessels
- Aorta connected to right ventricle and pulmonary artery to the left ventricle
- Therefore deoxygenated blood is going to the tissues and oxygenated to the lungs
- After birth, when the foramen ovale and ductus arteriosus close, the infant will become cyanotic and require treatment with prostaglandins and opening of the ductus arteriosus with eventual surgery
49
Describe the development of the lungs
- Embryonic
- Pseudoglandular
- Canalicular
- Saccular
- Alveolar
50
List the four cellular processes involved in embryological development
- Proliferation
- Differentiation
- Reorganisation
- Apoptosis
51
Describe gastrulation
- Gastrulation converts bilayer (epiblast and hypoblast) into a trilaminer embryo (ectoderm, mesoderm and endoderm) occuring days 14-18 postfertilisation
- Involves migration of cells between the epiblast and hypoblast layers, and differentiation of these cells
52
What is the function of the yolk sac?
- In humans, provides nutrients to the embryo early on
- This is then taken over by the placenta
- Lost by the second trimester
