week 1

Question 1

process of neural tube folding

Answer 1

the appearance of the notochord and mesoderm induces the overlying ectoderm to thicken and form the neural plate
after plate is induced it lengthens and lateral edges elevate
this forms the neural folds and the depressed midregion forms the neural groove
folds approach each other in the midline and fuse to form neural tube
tube sinks in and the overlying ectoderm repairs

Question 2

factors controlling neural plate bending

Answer 2

number of mechanisms control the bending:
cell wedging - microtubules and microfilaments change cell shape, cell cycle
hinge points are the most important - median hinge point and dorsalateral hinge points
extrinsic forces - pushing of surface ectoderm, adhesion point with notochord

Question 3

closure of the neural tube

Answer 3

fusion begins in the cervical region and proceeds in cephalic and caudal directions
open ends of the tube form the anterior and posterior neuropores and connect ith the overlying amniotic cavity
closure occurs in week 4, anterior by d25 and posterior by d27

Question 4

neural tube defects and how they occur

Answer 4

result of failure or incomplete closure of the neural tube
anterior neuropore - anencephaly
posterior neuropore - spina bifida

Question 5

spina bifidia occulta

Answer 5

symptomless but can be identified by a dimple or tuft of hair on level of incomplete closure of spinal cord

Question 6

spina bifida cystica - meningocoele

Answer 6

sac coming from the spinal cord which contains CSF and meninges
no neural tissue
covered by skin or meninge

Question 7

spina bifida cystica - myelomeningocoele

Answer 7

more severe complications - nerve damage and sometimes paralysis
sac contains part of spinal cord and nerve roots - can be damaged
surgery within hours of birth

Question 8

diagnosis of neural tube defects

Answer 8

raised levels of alpha-feto protein
ultrasound at 20 weeks
folic acid taken prior to conception and early stage of pregnancy can reduce chances

Question 9

differentiation of the neural tube

Answer 9

notochord continues to exert an inductive influence
presents the signalling molecule SHH to the neural tube
ventral-most cells respond to this signal and differentiate to make the floorplate of the neural tube
floorplate makes its own SHH and so will be responsible for development of motor neurons on each side of the tube

Question 10

role of sonic hedgehog (SHH)

Answer 10

critical role in development, patterning of the brain and spinal cord
roles in somite formation and limb bud formation
works at short range

Question 11

role of SHH in the formation of somite derivatives

Answer 11

causes cells in ventral part of somite to become sclerotime and undergo an epithelio-mesenchymal transformation
they can then migrate, move towards the signal source and form the verterbral cord around the notochord
SHH also affects the dermomyotome - induces competence to respond to signals from the surface ectoderm

Question 12

role of SHH in neural tube bending and closure

Answer 12

in the upper spine, dorsalateral hinge points are absent due to inhibition by BMP 2 - SHH expression is strong and inhibits noggin
in the lower spine, SHH is reduced and so noggin is uninhibited - it antagonises BMP 2 which allows DLHPs to form

Question 13

teratology

Answer 13

study of abnormal development of congenital defects

Question 14

teratogen

Answer 14

an agent that can disturb the development of an embryo or fetus

Question 15

teratogen definition

Answer 15

drugs and chemicals 
industrial pollutants 
hormones
infectious agents
mechanical factors

Question 16

how can antibiotics act as a teratogen

Answer 16

teracyclines cross the placenta and are deposited in bones and teeth at sites of calcification
teeth can become discoloured up until around 16 years of age
enamel formation affected
streptomycin - high doses cause inner ear defects

Question 17

drugs that can act as teratogens

Answer 17

epilepsy medication called disphenylhydantoin - causes fetal hydatoin syndrome - broad spectrum of cranialfacial defects, mental deficiencies
methotrexate - inhibits folic acid
antineoplastic drugs - designed to kill rapidly dividing cells
vitamin A - acne treatment - can cause affect facial structures, thymus and heart
warfarin - issues with bone development
aspirin - heart defects

Question 18

birth defects caused by alcohol

Answer 18

fetal alcohol syndrome:
facial deformities
low birth weight
small head circumference 
developmental delay
memory problems
behavioural problems
poor co-ordination
difficulty in socialisation skills

Question 19

how fetal alcohol syndrome develops

Answer 19

alcohol crosses placenta
fetal liver not fully developed and so cannot metabolise alcohol
fetus has high blood alcohol conc and so lacks oxygen and nutrients - white matter development effected
timing critical - facial features develop week 6-9
CNS develops all the way through so can be affected at any point

Question 20

timing of teratogens

Answer 20

pre-germ layer stage 1-2 weeks - death of embryo may occur
embryonic period 3-8 weeks - malformation of embryo may occur eg heart defect - period of maximal sensitivity - type of defect depends on which organ system is most vulnerable at that time
fetal period 9-38 weeks - functional disturbance of fetus may occur eg mental retardation

Question 21

decidualisation

Answer 21

in pregnancy, progesterone rises and causes stromal cells of the endometrium to become enlarged and accumulate glycogen
invading cells of the blastocyst are eroding the endometrium allowing blastocyst to burry into the endometrium
maternal vessels around the implantation site dilate
this is the uterus becoming receptive to pregnancy
endometrium is now called the decidua

Question 22

3 regions of decidua

Answer 22

decidua basalis - area that interacts with the fetal membranes
decidua capsularis - grows around the embryo that is bludging into the uterine lumen
decidua parietalis - rest of the decidua
capsularis and parietalis fuse around 20 weeks

Question 23

what is the chorion frondosum

Answer 23

fetal chorion in contact with the decidua basalis increases in size and complexity to become known as the chorion frondosum - goes on to form placenta

Question 24

villi formation

Answer 24

at day 13 primary villi appear

they are stalks of cytotrophoblast

Question 25

secondary villi fomation

Answer 25

by d16 extra embryonic mesoderm invades the core of the primary villi
secondary villi line the entire surface of the chorion

Question 26

tertiary villi formation

Answer 26

blood vessels develop in the mesenchyme of the secondary villi
these connect to the umbilical vessels of the embryo
villi that contain blood vessels are tertiary villli

Question 27

structure of placental barrier

Answer 27

4 layers thick:
fetal capillary endothelium
connective tissue of villi
synctiotrophoblast 
SCT layer lost in 4th month due to nutrient demand

Question 28

functions of the placenta

Answer 28

water crosses the placenta at 3.5 litres per hour in late pregnancy
maternal antibodies transfer to fetus giving passive immunity against diphtheria, small pox and measles - cross placenta by pinocytosis
protein hormones do not cross well although steroids do - passage of synthetic progestins and testosterone can lead to masculinisation of femal fetuses
drugs cross by diffusion
many viruses such as HIV and rubella can cross placental barrier

Question 29

what are extravillous trophoblasts

Answer 29

were cytotrophoblasts
invade into maternal endometrium, myometrium then spiral arteries
these cells remodel the coiled vessels from low flow, high resistance to become wider, high flow, low resistance channels
allows sufficient blood flow to fetus

Question 30

difference between maternal blood and fetal blood

Answer 30

maternal - rich in O2 and nutrients, flows from uterine arteries into large blood sinuses surrounding the villi then back into the uterine veins
fetal - low in nutrients and O2, flows through umbilical arteries to capillaries of the villi and returns through umbilical vein to the fetus

Question 31

how many umbilical arteries and veins are there

Answer 31

one umbilical vein and two arteries

Question 32

what is fetal growth restriction

Answer 32

failure to reach genetically pre-determined growth potential
increased risk of stillbirth, childhood morbidities and disease in adulthood
major cause is placental dysfunction

Question 33

what does the barker hypothesis explain

Answer 33

prenatal nutrition/fetal environment links to adulthood disease eg placental dysfunction is linked with obesity in adulthood

Question 34

pre-eclampsia

Answer 34

new-onset hypertension and proteinuria occurring after 20 weeks gestation
can occur with fetal growth restriction
left untreated can progress to eclamplsia which is life threatening - maternal seizures

Question 35

pre-eclampsia pathophyiology

Answer 35

incomplete remodelling of the spiral arteries
vessels remain narrow and blood supply is therefore reduced
ischaemia-reperfusion injury
impaired nutrient delivery

Question 36

what does the combined test screen for

Answer 36

downs syndrome (T21)
patau’s syndrome (T13)
edward’s syndrome (T18)
blood test and ultrasound

Question 37

chorionic villous sampling

Answer 37

sample from the placenta should contain the same chromosome complement as the fetus
carried out 11-14 weeks
1 in 100 risk of miscarriage

Question 38

amniocentesis

Answer 38

samples amniotic fluid which contains fetal cells
these cells can be grown in cell culture and fetal chromosomes are analysed to determine abnormalities associated with down’s syndrome and other genetic diseases such as cystic fibrosis
15 weeks
1 in 100 miscarry

Question 39

non-invasive prenatal testing

Answer 39

also known as cell free DNA screening
cell free fetal DNA migrate into maternal bloodstream via apoptotic trophoblast cells which have shed from placental tissue
maternal blood test after 10 weeks till the end of pregnancy
not diagnostic

Question 40

levels of PAPP-A in downs syndrome

Answer 40

low levels of PAPP-A