Embryology/Pregnancy (W1 KPH) Flashcards
what are the 3 stages of life before birth?
preimplantation stage (week 1)
embryonic stage: organogenesis (weeks 2-8)
fetal stage: growth/development (weeks 9-38)
what is embryological cleavage and what does it allow?
mitotic divisions of the fertilised oocyte (egg)
allows passage down narrowest part of the uterine tube (isthmus)
what cell specialisation does the oocyte have and what is its purpose?
surrounded by tough glycoprotein coat (zona pellucida) to prevent premature implantation
explain the process of morula formation
around day 4 after fertilisation, cells maximise contact with eachother, forming a cluster of cells held together by tight junctions
it then enters the uterus
what are the first signs of cellular differenciation?
blastocyst formation
what occurs during blastocyst formation?
inner cell mass - forms embryo and extraembryonic tissues
outer cells (trophoblasts) - contributes to placenta
fluid filled blastocyst cavity also forms
explain the process of blastocyst hatching
ICM cells undergo proliferation and fluid fills up in the cavity, resulting in the blastocyst hatching from the zona pellucida to facilitate implantation
explain the process of decidualisation
occurs in uteral stromal cells, is the process of several endometrium (part of uterus) changes in preparation for pregnancy
what happens to trophoblasts during decidualisation?
they become invasive and begin to differenciate
what are the 2 differenciated trophoblast layers called and which one is invasive?
inner - cytotrophoblast
outer - syncytiotrophoblast (invasive)
what do implanting syncytiotrophoblasts do at the end of week 2?
communication with maternal placenta side to establish a connection
enables diffusion of oxygen, nutrients and waste through blood supply
what hormone does syncytiotrophoblasts produce?
where is it secreted?
human chorionic gonadotrophin (hCG)
secreted into urine
what is an ectopic implantation?
where zygote implantation occurs in the wrong place
what could cause an ectopic pregnancy?
slow transit through uterine tube or premature blastocyst hatching
where can ectopic implantations implant?
uterine tube, peritoneal cavity or ovary surface
name the 4 extra-embryonic membranes
amnion
chorion
yolk sac
allantois
describe the key features of the amnion
continuous with epiblasts on bilaminar disc
lines amniotic cavity which is filled with fluid and protects the embryo
presents up until birth
describe the key features of the chorion
doubled layered membrane formed by trophoblasts/extraembryonic mesoderm (EEM)
lines chorionic cavity, seen in early pregnancy but disappears due to amniotic cavity
forms fetal component of placenta
describe the key features of the yolk sac
continuous with hypoblasts on bilaminar disc
important in week 2-3 nutrient transfer, dissapears by week 20
important in blood cell and gut formation
describe the key features of the allantois
outgrowth of yolk sac
contributes to umbilical arteries and connects to fetal bladder
define gastrulation
a process of cell division and migration resulting in the formation of 3 germ layers
what forms from the bilaminar epiblast in week 3?
trilaminar embryo
what are the 3 germ layers called?
ectoderm, mesoderm and endoderm
what additional structures are important in week 3 development?
primitive streak, notochord, neural tube
what is the primitive streak?
a thickened area of cells originating from the embryo’s tail end
what growth factor is made by the primitive streak?
fibroblast GF 8
describe some of the structures the ectoderm forms
generally outer structures:
epidermis, hair follicles, epithelial lining of mouth/anus, cornea, adrenal medulla, nervous system
describe the structures formed by the mesoderm
generally central structures:
MSK, circulatory/lymphatic systems, dermis of skin, adrenal cortex
describe the structures formed by the endoderm
generally inner linings and organs:
liver, pancreas, epithelial digestive tract lining, thyroid/parathyroid glands
what does the mesoderm layer divide into once formed?
notochord
paraxial mesoderm
intermediate mesoderm
lateral mesoderm
extraembryonic mesoderm
what are the 2 areas of the early embryo without mesoderm?
oropharyngeal membrane and cloacal membrane
what days are the paraxial, intermediate and later plate mesoderm formed between?
17-21
describe the formation, location and differenciations of the paraxial mesoderm
forms from cells moving bilaterally and cranially from primitive streak
lies adjacent to notochord and neural tube
forms somites in the embryo
what does the intermediate mesoderm form?
GU system
what 2 layers is the lateral plate mesoderm split into and what splits it?
split by cavity (intraembryonic coelom)
forms somatic (parietal) and splanchnic (visceral) layer
which mesoderm layer does each muscle type arise from?
skeletal - paraxial
smooth/cardiac - visceral lateral plate
explain the formation of somites from paraxial mesoderm
paraxial mesoderm arranged into somites (segments)
forms alongside neural tube in a craniocaudal sequence
somites appear 3 pairs a day from day 20 until 5 weeks
what happens to unsegmented mesoderm?
called pre-somitic mesoderm
gets ‘patterned’
explain the gene regulation of somite formation
as somites form, gene notch is high and it moves down the embryo from the bottom
FGF8 gene washes up somites
the overlapping gradients control somite formation
what happens when somites lose their epithelial characteristics?
segmented paraxial mesoderm is transformed into spheres forming an epithelial cell lumen
occurs in week 4 when cells undergo epithelial-mesenchymal transition
what happens to cells in the ventral half of a somite?
they undergo epithelial-mesenchymal transition
the become the sclerotome and form the vertebrae and ribs
what happens to cells in the dorsal half of somites?
they become the dermomyotome
this splits into the dermatome (dermis of the back) and myotome (muscles)
what does the parietal layer of the lateral plate mesoderm form?
body wall, CT and bones
what does the visceral layer of the lateral plate mesoderm form?
the tube of gut wall and serous membranes
what occurs when myoblasts align with chains and fuse?
what mediates this?
cell membranes disappear creating multinucleated myotubules (primary tubules)
myogenin mediates this differenciation
explain the role of muscle specific gene activator transcription factors (with examples)
enables differenciation of myogenic precursor cells in the dermomyotome of myoblasts
converts non-muscle cells (fibroblasts/adipocytes) into cells expressing muscle proteins (essentially muscle cells)
e.g MYOD and MYF5
how is MYOD and MYF5 expressed in the neural tube?
WNT proteins (activating) and BMP proteins (inhibitory) combine to activate MYOD in the dermomyotome
this creates muscle cell precursors which express MYF5
what induces sclerotome formation in the notochord?
sonic hedgehog and noggin
name the 2 locations MYOD and MYF5 can be expressed?
neural tube and lateral plate mesoderm
explain the process of embryonic folding and when it occurs
split into lateral folding (by somites) and cephalocaudal folding (by CNS)
occur simultaneously and closes body wall of embryo creating a tube structure
occurs days 18-21
explain mesenchymal stem cells role in intramembranous ossification
begins with condensation of mesenchymal cells which proliferate and differenciate into osteoprogenitor cells which turn into osteoblasts (allowing cartilage step to be skipped)
explain the characteristics of the notochord
transient patterning structure
role in molecular signalling
controls embryonic folding direction
flexible rod-shaped structure ventral to neural tube
inductive relationship with overlying ectoderm
what does the notochord become after birth?
nucleus puplosus of the intervertebral disc
what do the signals arising from the notochord do?
induce development in neural plate and overlying ectoderm
what are the 2 important notochord signals and what do they do?
noggin and chordin
negative regulators - presence activates inhibition of other molecules
they inactivate BMPs (BMP4) which allows patterning of neural tube and somites
explain the formation of the neural plate
appearance of the notochord and mesoderm induces overlying ectoderm to thicken (forming neural plate)
cells of the plate make up the neuroectoderm (the initial event of neurulation)
explain how the neural tube is formed from the neural plate
neural plate lengthens and lateral edges elevate
the elevation makes 2 neural folds and the depression in the centre creates the neural groove
the folds move towards eachother and fuses in the middle creating the tube
what happens to the neural tube after formation and what will it go on to form?
neural tube sinks into embryo body
surface ectoderm repairs over the top of tube
will go on to form the brain and spinal cord
what mechanisms control the bending of the neural plate?
cell wedging - microtubules/microfilaments change cell shape
hinge points - median and dorsolateral
extrinsic forces - pushing of surface ectoderm, adhesion point with notochord
what are neural crest cells?
migratory cells forming during neurulation
move through embryo body forming various structures (e.g dorsal root ganglia and teeth)
explain the closure of the neural tube
cervical fusion occurs in caudal and cephalic directions
open tube ends form anterior and posterior neuropores (connect with overlying amniotic cavity)
occurs in week 4 (anterior day 25, posterior day 27)
name the 3 known causes of congenital issues
environmental
chromosomal
multifactorial genetic predisposition (with environment correct for expression)
name some minor congenital defects
pigmented spots
small ears
what is a teratogen?
an agent/substance that can disturb the development of an embryo/fetus
what will occur during teratogen exposure in weeks 1-2 of development?
either nothing or spontaneous abortion
what will occur during teratogen exposure from weeks 3-8?
teratogens highly effective
defect seen depends on which organ system is most vunerable at time of development when teratogen acts
what will occur during teratogen exposure from weeks 9-38?
functional deficits and minor abnormalities as susceptibility is reduced
what 2 organ systems remain vunerable to teratogen exposure through all weeks of gestation?
GU and CNS
explain the effect of sonic hedgehog from the notochord on the neural tube
notochord presents SHH to adjacent neural tube, where the ventral-most cells respond, creating the neural tube floorplate
floorplate now makes its own SHH which develops motor neurones on each side of the tube
describe the characteristics of sonic hedgehog (SHH)
powerful and widespread
works at short range
critical role in development/patterning of the brain and spinal cord
also has roles in somite patterning and limb bud development
what can SHH signal in ventral somite sclerotome?
signals it to undergo epithelio-mesenchymal transformation
how are dorsolateral hinge points only seen in some regions of the spine?
upper spine - DLHPs absent due to BMP2 inhibition, SHH expression is strong inhibiting noggin
lower spine - SHH is reduced so noggin is uninhibited, it antagonises BMP2 which allows DLHPs to form
what are the 5 classifications of teratogens?
drugs/chemicals
industrial pollutants
hormones
infectious agents
mechanical factors
name different types of drug that can be teratogenic and an example of each
antibiotics - streptomycin
non-prescription painkillers - paracetamol
DMARDs - methotrexate
name which hormones can be teratogenic and what they defect
androgens - masculinisation of female genitalia
endocrine disruptors (synthetic oestrogens) - increased carcinoma
explain the mechanism of fetal alcohol syndrome development
alcohol crosses placenta -> fetal liver cant metabolise alcohol -> high blood alcohol conc. in fetus -> lack of o2 and nutrients -> white matter development affected
how does the embryo receive nutrition before the placenta develops?
diffusion
what are trophoblastic lacunae?
spaces where syncytiotrophoblastic activity has eroded
what happens to the enlarged blood vessels in the embryonic implantation?
they fill the spaces in the syncytiotrophoblast layer merging the maternal and fetal blood supply
what are villi on the zygote?
stalks of cytotrophoblast that appear at day 13
what occurs to villi at around day 16?
extra-embryonic mesoderm (chorionic) invades the primary villi core
they become secondary villi that line the surface of the chorion
what occurs to secondary villi?
blood vessels develop in mesenchyme (they become tertiary villi)
they connect to umbilical vessels of embryo
what is the placental barrier?
partition between maternal and fetal circulation
it is initially 4 layers thick (reduces to 3 in month 4)
what are the 4 layers of the placental barrier?
fetal capillary endothelium
CT of villi
cytotrophoblast
syncytiotrophoblast
what are the main functions of the placenta?
metabolism - synthesises glycogen, cholestorol, fatty acids, nutrients
transfer - o2, co2, urea, uric acid, bilirubin
amino acid transfer by carrier mechanism
vitamins B/C/D cross readily
name all the blood vessels present in the placenta
maternal artery, maternal vein, 2x umbilical arteries, umbilical vein, chorionic vessels
what are the basic functions of the placental membrane?
separates maternal and fetal blood, allows substance diffusion
what is present in the intervillous spaces in the placenta?
pools of maternal blood
what is the function of wharton’s jelly?
protects umbilical vessels from damage
what enters the trophoblastic lacunae to support the developing placenta?
glandular secretions and spiral arteries
what are interstitial extravillous trophoblasts?
cytotrophoblast cells that have left the trophoblast
they invade the endometrial blood vessels, blocking them
explain what extravillous trophoblast cells do after invading the spiral arteries
remodel the coiled vessels from low flow-high resistance to wider high flow-low resistance channels
this allows sufficient blood flow to fetus
explain the process of maternal blood flow through the placenta
blood enters the villous trees and enter the intervillous space coming in close contact with fetal blood without mixing
how does maternal blood supply nutrients?
flows from uterine arteries into large blood sinuses surrounding villi, then back into uterine veins
how does fetal blood transfer nutrients?
flows through umbilical arteries to capillaries in villi and returns through umbilical vein to fetus
what are the 4 mechanisms in which nutrients travel across the placenta?
diffusion
paracellular diffusion
transporter-mediated transfer
endocytosis/exocytosis
name molecules that travel across the placenta
O2, CO2, H2O, HCO3, glucose, amino acids, lipids, fatty acids, vitamins B/C
immunoglobulins (IgG not IgM)
what does human chorionic gonadotrophin do?
maintains corpus luteum in ovary
allows oestrogen, placental lactogen and progestorone production in corpus lutem before placenta develops
name pathogens that can cross the placenta that would cause harm
bacteria - listeria
protozoa - plasmodium falciparum (causes malaria) and toxoplasma gondii (cat feces produces it)
viruses - zika, rubella, cytomegalovirus
define miscarriage and stillbirth
loss of a pregnancy during the first 23 weeks of pregnancy
(after 13 weeks = late miscarriage)
stillbirth is the death of a baby after 24 weeks of gestation
what is fetal growth restriction?
failure to reach genetically pre-determined growth potential
birth weight before 5th percentile of growth charts
what is the cause and risks of fetal growth restriction?
cause - placental dysfunction
risks - childhood morbility, stillbirth, adult disease
explain the basics of the barker hypothesis
assesses the correlation of prenatal nutrition and fetal environment to adulthood disease
what is pre-eclampsia?
new onset hypertension (above 140/90) and proteinuria occuring after 20 weeks gestation
if left untreated = elcampsia (maternal seizures)
explain the pathophysiological result of pre-eclampsia
vessels remain narrow and blood supply is reduced
ischaemia-reperfusion injury
impaired nutrient delivery
explain the maturation of the lungs during pregnancy
lungs are filled with fluid which is expulsed during breathing movements into the amniotic sac via the trachea
explain the function of pulmonary surfactant in lung maturation
secretes by type 2 pheumocytes at 24 weeks gestation
facilitates lung expansion at birth and reduces surface tension
enough produced to support gas exchange after 35 weeks
explain the mechanisms of the renal system maturation
new nephrons formed until 36 weeks gestation
kidneys produce dilute urine but placenta fulfils most of their role
how much amniotic fluid does a fetus swallow?
7ml per hour
how much urine does a fetus produce?
300ml/kg per day
what is associated with poor renal function in fetuses?
oligohydraminos (too little amniotic fluid)
what is produced in the process of digestive tract maturation?
maturation of enzymes for digestion and absorption occurs
crypts and villi develop from weeks 8-24 gestation that elongate with time
what is meconium?
greenish mixture of shed intestinal cells, lanugo, mucous and amniotic fluid
baby’s first poo
explain the physiological features of fetal circulation maturation
haemopoiesis in the fetal liver becomes dominant from the second trimester
most erythrocytes contain fetal haemoglobin (hbF) which has a greater affinity for oxygen than adult haemoglobin
why is the adrenal cortex in a fetus very large?
adrenal gland produces steriod precursor for oestrogen biosynthesis by the placenta
explain the role of the fetal posterior pituitary gland
secretes oxytocin from second trimester onwards
levels rise during labour to initiate contractions
what maternal adaptations occur to support a pregnancy?
RR and tidal volume increase - increase gas exchange
maternal blood volume increases by 50%
nutrient requirements increase
glomerular filtrartion increases by 50%
explain how the maternal blood volume increases during pregnancy
placenta removes blood from systemic circulation
erythropoetin and renin production induced to increase blood volume
explain how oestrogen is produced and maintains pregnancy
stimulates labour/birth
produced by fetus and placenta cooperation
fetal adrenal gland secretes androgens which are converted to oestrogen by placenta
what is the functions of human placental lactogen (hPL) in maintaining pregnancy?
promotes growth/differenciation of mammary glands (lactation tissues)
stimulates maternal tissues to ensure glucose and protein available to fetus
what is the function of relaxin in supporting a pregnancy?
increases pubic symphysis flexibility and cervix dilation
suppresses oxytocin by hypothalamus delaying labour contractions
what is the functions of placental growth hormone in maintaining a pregnancy?
suppresses/replaces maternal GH
enhances nutrient availability to fetus by stimulating lipolysis and gluconeogenesis
what is partuition and how does it occur?
childbirth
series of strong rhythmic uterine contractions (labour)
what fetal and maternal endocrine changes occur during labour?
progestorone levels reduced
fetal pituitary secretes oxytocin entering maternal blood stream
maternal pituitary secretes oxytocin
prostoglandin produced by fetal membranes (as well as oestrogen and oxytocin)
explain labour contractions and how it is a positive feedback system
contractions begin at superior uterus towards cervix and increase in force and frequency
stretching of cervix further stimulates oxytocin release
explain the first step of parturition
dilation:
cervical softening and dilation
myometrial contractions increase frequency
amniochorionic membrane ruptures
cervix dilates to ~10cm
explain the second stage of parturition
expulsion:
contractions strong/frequent
urge to push baby out
may need episiotomy (peritoneum cut to avoid tearing)
how is neonatal health assessed and what is assessed?
APGAR score
A - appearance (colour)
P - pulse (HR)
G - grimace (reflex irritability)
A - activity (muscle tone)
R - respiratory effort
explain the third stage of parturition
placental:
can either be removed by midwife using oxytocin injection (active) or delivered postpartum using contractions (physiological)
what are some of the common terminologies used in describing embryological defects?
atresia - absense or narrowing of an opening
agenesis - failure of an organ part to develop
what are the defects of babies with VACTERL?
V - vertebrae/ribe
A - anorectal
C - cardiac
T - tracheo-oesophageal fistula
A - esophageal atresia
R - renal anomaly
L - limb anomaly
